{"id":658904,"date":"2026-10-19T01:20:13","date_gmt":"2026-10-19T01:20:13","guid":{"rendered":"https:\/\/www.newsbeep.com\/ie\/658904\/"},"modified":"2026-10-19T01:20:13","modified_gmt":"2026-10-19T01:20:13","slug":"oncogenic-mutations-in-non-small-cell-lung-cancer-from-molecular-mechanisms-to-clinical-practice","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ie\/658904\/","title":{"rendered":"Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice"},"content":{"rendered":"

Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229\u2013263 (2024).<\/p>\n

PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kris, M. G. et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311, 1998 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Meyer, M.-L. et al. New promises and challenges in the treatment of advanced non-small-cell lung cancer. Lancet 404, 803\u2013822 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tan, A. C. & Tan, D. S. W. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J. Clin. Oncol. 40, 611\u2013625 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drusbosky, L. M., Dawar, R., Rodriguez, E. & Ikpeazu, C. V. Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer. J. Hematol. Oncol. 14, 129 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bria, E. et al. Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis. Ann. Oncol. 22, 2277\u20132285 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Herbst, R. S. et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non\u2013small-cell lung cancer: updated results from the phase III randomized ADAURA trial. J. Clin. Oncol. 41, 1830\u20131840 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhong, W.-Z. et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC: final overall survival analysis of CTONG1104 phase III trial. J. Clin. Oncol. 39, 713\u2013722 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhong, W.-Z. et al. Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial. Signal Transduct. Target. Ther. 8, 76 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. Alectinib in resected ALK -positive non\u2013small-cell lung cancer. N. Engl. J. Med. 390, 1265\u20131276 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zenke, Y. et al. P1.18-04 neoadjuvant ceritinib for locally advanced non-small cell lung cancer with ALK rearrangement: SAKULA trial. J. Thorac. Oncol. 14, S626\u2013S627 (2019).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Miyoshi, T. & Tsuboi, M. Postoperative adjuvant therapy with molecularly targeted agents for non-small cell lung cancer. Int. J. Clin. Oncol. 30, 210\u2013214 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Akamatsu, H. Gefitinib with concurrent thoracic radiotherapy in unresectable locally advanced NSCLC with EGFR mutation; West Japan Oncology Group 6911L. J. Thorac. Oncol. 16, 1745\u20131752 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hotta, K. et al. Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902\/OLCSG0905 phase II study. ESMO Open 6, 100191 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bai, X. et al. Structure and dynamics of the EGFR\/HER2 heterodimer. Cell Discov. 9, 18 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, R. et al. Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma. Cell Death Dis. 9, 36 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 18, 1454\u20131466 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rangachari, D. et al. Brain metastases in patients with EGFR -mutated or ALK -rearranged non-small-cell lung cancers. Lung Cancer 88, 108\u2013111 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Offin, M. et al. Frequency and outcomes of brain metastases in patients with HER2 -mutant lung cancers. Cancer 125, 4380\u20134387 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Patil, T. et al. The incidence of brain metastases in stage IV ROS1-rearranged non\u2013small cell lung cancer and rate of central nervous system progression on crizotinib. J. Thorac. Oncol. 13, 1717\u20131726 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Long, J. et al. Efficacy and safety of original EGFR-TKI combined with bevacizumab in advanced lung adenocarcinoma patients harboring EGFR-mutation experiencing gradual progression after EGFR-TKI treatment: a single-arm study. Ann. Transl. Med. 10, 1334 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. K. et al. First-line icotinib versus cisplatin\/pemetrexed plus pemetrexed maintenance therapy for patients with advancedEGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann. Oncol. 28, 2443\u20132450 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 15, 213\u2013222 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. CNS efficacy of osimertinib in patients with T790M-positive advanced non\u2013small-cell lung cancer: data from a randomized phase III trial (AURA3). J. Clin. Oncol. 36, 2702\u20132709 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mok, T. S. et al. Osimertinib or platinum\u2013pemetrexed in EGFR T790M\u2013positive lung cancer. N. Engl. J. Med. 376, 629\u2013640 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Papadimitrakopoulou, V. A. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann. Oncol. 31, 1536\u20131544 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Majem, M. et al. First-line osimertinib in patients with epidermal growth factor receptor\u2013mutant non\u2013small-cell lung cancer and with a coexisting low allelic fraction of Thr790Met. Eur. J. Cancer 159, 174\u2013181 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Reungwetwattana, T. et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR -mutated advanced non\u2013small-cell lung cancer. J. Clin. Oncol. 36, 3290\u20133297 (2018).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Soria, J.-C. et al. Osimertinib in untreated EGFR -mutated advanced non\u2013small-cell lung cancer. N. Engl. J. Med. 378, 113\u2013125 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR -mutated advanced NSCLC. N. Engl. J. Med. 382, 41\u201350 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Leighl, N. B. et al. Patient-reported outcomes from FLAURA: osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer. Eur. J. Cancer 125, 49\u201357 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Efficacy of aumolertinib (HS-10296) in patients with advanced EGFR T790M+ NSCLC: updated post-national medical products administration approval results from the APOLLO registrational trial. J. Thorac. Oncol. 17, 411\u2013422 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Aumolertinib activity in patients with CNS metastases and EGFR-mutated NSCLC treated in the randomized double-blind phase III trial (AENEAS). J. Clin. Oncol. 40, 9096 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastaticnon\u2013small-cell lung cancer with EGFR Exon 19 deletion or L858R mutations. J. Clin. Oncol. 40, 3162\u20133171 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yun, J. et al. YH25448, an irreversible EGFR-TKI with potent intracranial activity in EGFR mutant non\u2013small cell lung cancer. Clin. Cancer Res. 25, 2575\u20132587 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, B. C. et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR -mutated advanced non\u2013small-cell lung cancer: results from LASER301. J. Clin. Oncol. 41, 4208\u20134217 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Soo, R. A. et al. Central nervous system outcomes of lazertinib versus gefitinib in EGFR-mutated advanced NSCLC: a LASER301 subset analysis. J. Thorac. Oncol. 18, 1756\u20131766 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, B. C. et al. A Phase 1\/2 study of lazertinib 240 mg in patients with advanced EGFR T790M-positive NSCLC after previous EGFR tyrosine kinase inhibitors. J. Thorac. Oncol. 17, 558\u2013567 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jang, S. B. et al. Cardiac safety assessment of lazertinib: findings from patients with EGFR mutation-positive advanced NSCLC and preclinical studies. JTO Clin. Res. Rep. 2, 100224 (2021).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study. Lancet Respir. Med. 9, 829\u2013839 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Central nervous system efficacy of furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR-mutated NSCLC: results from the FURLONG study. J. Thorac. Oncol. 17, 1297\u20131305 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir. Med. 10, 1019\u20131028 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahn, M.-J. et al. Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion study. Lancet Respir. Med. 5, 891\u2013902 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, Q. et al. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: the phase 3 EVEREST trial. Med 6, 100513 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Maggie Liu, S.-Y. et al. Efficacy, safety and dose selection of AZD3759 in patients with untreated EGFR-mutated non-small-cell lung cancer and central nervous system metastases in China (CTONG1702-Arm 8): a multi-center, single-arm, phase 2 trial. eClinicalMedicine 64, 102238 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respir. Med. 11, 905\u2013915 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. LBA9 Final overall survival (OS) results of befotertinib in patients with pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Ann. Oncol. 34, S1654 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Efficacy and safety of befotertinib (D-0316) in patients with EGFR T790M-mutated NSCLC that had progressed after prior EGFR tyrosine kinase inhibitor therapy: a phase 2, multicenter, single-arm, open-label study. J. Thorac. Oncol. 17, 1192\u20131204 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Efficacy and Safety of Limertinib (ASK120067) in patients with locally advanced or metastatic EGFR Thr790Met-mutated NSCLC: a multicenter, single-arm, phase 2b study. J. Thorac. Oncol. 17, 1205\u20131215 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Efficacy and safety of rezivertinib (BPI-7711) in patients with locally advanced or metastatic\/recurrent EGFR T790M-mutated NSCLC: a phase 2b study. J. Thorac. Oncol. 17, 1306\u20131317 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study. Lancet Respir. Med. 13, 327\u2013337 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, C. & Xiong, A. OA02.04 A phase III study of rilertinib versus gefitinib as first-line therapy for patients with locally advanced or metastatic EGFR-mutated NSCLC. J. Thorac. Oncol. 19, S11 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, S., Tsui, S. T., Liu, C., Song, Y. & Liu, D. EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J. Hematol. Oncol. 9, 59 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, X. et al. Targeting EGFRL858R\/T790M and EGFRL858R\/T790M\/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry. Med. Res. Rev. 38, 1550\u20131581 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Elamin, Y. Y. et al. BLU-945 monotherapy and in combination with osimertinib (OSI) in previously treated patients with advanced EGFR-mutant (EGFRm) NSCLC in the phase 1\/2 SYMPHONY study. J. Clin. Oncol. 41, 9011 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lim, S. M. et al. BBT-176, a novel fourth-generation tyrosine kinase inhibitor for osimertinib-resistant EGFR mutations in non\u2013small cell lung cancer. Clin. Cancer Res. 29, 3004\u20133016 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, C. et al. Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR Exon 20 insertion\u2013positive metastatic non\u2013small cell lung cancer: a phase 1\/2 open-label nonrandomized clinical trial. JAMA Oncol. 7, e214761 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, M. et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial. Lancet Respir. Med. 12, 217\u2013224 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Han, B. et al. OA03.04 A phase 1b study of furmonertinib, an oral, brain penetrant, selective EGFR inhibitor, in patients with advanced NSCLC with EGFR exon 20 insertions. J. Thorac. Oncol. 18, S49 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yu, H. A. et al. Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. J. Clin. Oncol. 43, 8503 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

J\u00e4nne, P. A. et al. First-line mobocertinib versus platinum-based chemotherapy in patients with EGFR exon 20 insertion\u2013positive metastatic non\u2013small cell lung cancer in the phase III EXCLAIM-2 trial. J. Clin. Oncol. 43, 1553\u20131563 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Elamin, Y. Y. et al. Poziotinib for EGFR exon 20-mutant NSCLC: clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity. Cancer Cell 40, 754\u2013767.e6 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Piotrowska, Z. Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions. Ann. Oncol. 29, 2092\u20132097 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, S. V. et al. LBA61 First analysis of RAIN-701: study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1\/ERBB gene fusions. Ann. Oncol. 31, S1189 (2020).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, J. C.-H. et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 16, 830\u2013838 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sato, Y. et al. Survival outcomes and subgroup analyses derived from a phase III randomized trial comparing afatinib to chemotherapy in treatment-na\u00efve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation (ACHILLES\/TORG1834). J. Clin. Oncol. 42, 8588 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, J. H. et al. Osimertinib for patients with non\u2013small-cell lung cancer harboring uncommon EGFR mutations: a multicenter, open-label, phase II trial (KCSG-LU15-09). J. Clin. Oncol. 38, 488\u2013495 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Borgeaud, M. et al. Unveiling the landscape of uncommon EGFR mutations in NSCLC-A systematic review. J. Thorac. Oncol. 19, 973\u2013983 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fang, W. F. et al. 57P: safety and efficacy of aumolertinib treatment in patients with advanced NSCLC harboring 20ins and uncommon EGFR mutations (AIM). J. Thorac. Oncol. 20, S45\u2013S46 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Robichaux, J. P. et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 597, 732\u2013737 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wells, L. & Qin, A. Treatment of non-small cell lung cancer with atypical EGFR mutations. Curr. Treat. Options Oncol. 24, 1802\u20131814 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Le, X. et al. PL04.07 FURTHER: a global, randomized study of firmonertinib at two dose levels in TKI-naive, advanced NSCLC with EGFR PACC mutations. J. Thorac. Oncol. 19, S5\u2013S6 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Brazel, D. & Nagasaka, M. The development of amivantamab for the treatment of non-small cell lung cancer. Respir. Res. 24, 256 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, B. C. et al. Amivantamab plus lazertinib in previously untreated EGFR -mutated advanced NSCLC. N. Engl. J. Med. 391, 1486\u20131498 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, C. et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N. Engl. J. Med. 389, 2039\u20132051 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, J. et al. Efficacy and safety of MCLA-129, an EGFR\/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC). J. Clin. Oncol. 42, 8604 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cappuzzo, F. et al. 516MO Efficacy and safety of MCLA-129, an anti-EGFR\/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC). Ann. Oncol. 34, S1671 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Planchard, D. et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N. Engl. J. Med. 389, 1935\u20131948 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

J\u00e4nne, P. A. et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor\u2013mutated advanced non\u2013small-cell lung cancer. J. Clin. Oncol. 42, 808\u2013820 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tanaka, K. et al. Osimertinib versus osimertinib plus chemotherapy for non\u2013small cell lung cancer with EGFR (T790M)-associated resistance to initial EGFR inhibitor treatment: an open-label, randomised phase 2 clinical trial. Eur. J. Cancer 149, 14\u201322 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Abstract CT053: Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2). Cancer Res. 85, CT053 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Passaro, A. et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann. Oncol. 35, 77\u201390 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bauml, J. et al. Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-na\u00efve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response. J. Clin. Oncol. 39, 9006 (2021).<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhao, S. et al. Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer. Nat. Commun. 14, 3468 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gettinger, S. et al. Nivolumab plus erlotinib in patients with EGFR-mutant advanced NSCLC. J. Thorac. Oncol. 13, 1363\u20131372 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Oxnard, G. R. et al. TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. Ann. Oncol. 31, 507\u2013516 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Alexander, M. et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated non-small cell lung cancer: patient satisfaction and resource utilization results from the PALOMA-3 study. Eur. J. Cancer 227, 115624 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mayer, C. et al. Direct identification of ALK and ROS1 fusions in non-small cell lung cancer from hematoxylin and eosin-stained slides using deep learning algorithms. Mod. Pathol. 35, 1882\u20131887 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Horn, L. et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase\u2212positive non\u2013small cell lung cancer: a randomized clinical trial. JAMA Oncol. 7, 1617 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Costa, D. B. et al. Clinical experience with crizotinib in patients with advanced ALK -rearranged non\u2013small-cell lung cancer and brain metastases. J. Clin. Oncol. 33, 1881\u20131888 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shaw, A. T. et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 18, 874\u2013886 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wolf, J. et al. Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. ESMO Open 7, 100333 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, J. C.-H. et al. Brigatinib versus alectinib in ALK-positive NSCLC after disease progression on crizotinib: results of phase 3 ALTA-3 trial. J. Thorac. Oncol. 18, 1743\u20131755 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, Y. et al. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir. Med. 8, 45\u201353 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Peters, S. et al. Alectinib versus crizotinib in untreated ALK -positive non\u2013small-cell lung cancer. N. Engl. J. Med. 377, 829\u2013838 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Camidge, D. R. et al. Brigatinib versus crizotinib in ALK inhibitor\u2013naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J. Thorac. Oncol. 16, 2091\u20132108 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Soria, J.-C. et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet 389, 917\u2013929 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mok, T. et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann. Oncol. 31, 1056\u20131064 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Iruplinalkib (WX-0593) versus crizotinib in ALK TKI-naive locally advanced or metastatic ALK-positive NSCLC: interim analysis of a randomized, open-label, phase 3 study (INSPIRE). J. Thorac. Oncol. 19, 912\u2013927 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y.-K. et al. 1278P Update of the INSPIRE study: iruplinalkib versus crizotinib in ALK TKI-na\u00efve locally advanced or metastatic ALK+ non-small cell lung cancer (NSCLC). Ann. Oncol. 35, S815 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT). BMC Med. 21, 72 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. P1.12B.07 iruplinalkib in patients with ALK-positive crizotinib-resistant NSCLC: updated efficacy and safety data from a phase 2 trial. J. Thorac. Oncol. 19, S203 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, Y. et al. Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial. Signal Transduct. Target. Ther. 8, 301 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xiong, A. et al. OA09.03 Randomized, open-label, phase III study of SAF-189s versus crizotinib in first-line ALK-positive advanced non-small cell lung cancer (NSCLC). J. Thorac. Oncol. 19, S27\u2013S28 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Han, B. et al. P2.01-31 preliminary results of second generation ALK inhibitor PLB1003: a phase La study. J. Thorac. Oncol. 14, S651 (2019).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xing, P. et al. Conteltinib (CT-707) in patients with advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, first-in-human phase 1 study. BMC Med. 20, 453 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zou, H. Y. et al. PF-06463922 is a potent and selective next-generation ROS1\/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc. Natl. Acad. Sci. 112, 3493\u20133498 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Solomon, B. J. et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 19, 1654\u20131667 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Solomon, B. J. et al. Lorlatinib versus crizotinib in patients with advanced ALK-positive non\u2013small cell lung cancer: 5-year outcomes from the phase III CROWN study. J. Clin. Oncol. 42, 3400\u20133409 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, D. et al. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann. Oncol. 31, 1207\u20131215 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, J. J. et al. NVL-655 is a selective and brain-penetrant inhibitor of diverse ALK-mutant oncoproteins, including lorlatinib-resistant compound mutations. Cancer Discov. 14, 2367\u20132386 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Solomon, B. J., Millward, M., Kim, D.-W., Park, E. K. & Lin, J. J. 1363TiP A phase I\/II study of TPX-0131, a novel oral ALK tyrosine kinase inhibitor, in patients with ALK+ advanced\/metastatic NSCLC. Ann. Oncol. 32, S1034 (2021).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Johnson, M. L. et al. 81TiP NVL-655, a selective anaplastic lymphoma kinase (ALK) inhibitor, in patients with advanced ALK-positive solid tumors: The phase I\/II ALKOVE-1 study. J. Thorac. Oncol. 18, S86\u2013S87 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. E. et al. 1253O Phase I\/II ALKOVE-1 study of NVL-655 in ALK-positive (ALK+) solid tumours. Ann. Oncol. 35, S802\u2013S803 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cheng, Y., Yang, J., Wang, D. & Yan, D. ROS1 fusion lung adenosquamous carcinoma patient with short-term clinical benefit after crizotinib treatment: a case report. Ann. Transl. Med. 10, 157 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shaw, A. T. et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann. Oncol. 30, 1121\u20131126 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1\u20132 trials. Lancet Oncol. 21, 261\u2013270 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Long-term efficacy and safety of entrectinib in ROS1 fusion\u2013positive NSCLC. JTO Clin. Res. Rep. 3, 100332 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Peters, S. Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2\/3 BFAST trial. Nat. Med. 30, 1923\u20131932 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lim, S. M. et al. Open-label, multicenter, phase II study of ceritinib in patients with non\u2013small-cell lung cancer harboring ROS1 rearrangement. J. Clin. Oncol. 35, 2613\u20132618 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, J.-J. et al. Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study. Lancet Respir. Med. 12, 671\u2013680 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Niho, S. et al. Phase II study of brigatinib in patients with ROS1 fusion-positive non-small-cell lung cancer: the Barossa study. ESMO Open 9, 103642 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Guo, R. et al. P1.14-50 a phase 2 trial of cabozantinib in ROS1-rearranged lung adenocarcinoma. J. Thorac. Oncol. 14, S574\u2013S575 (2019).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Girard, N. et al. Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study. ESMO Open 7, 100418 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shaw, A. T. et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1\u20132 trial. Lancet Oncol. 20, 1691\u20131701 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahn, B. C. et al. Lorlatinib in TKI na\u00efve, advanced ROS1-positive non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 trial. J. Clin. Oncol. 42, 8519 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

P\u00e9rol, M. et al. Taletrectinib in ROS1 + non\u2013small cell lung cancer: TRUST. J. Clin. Oncol. 43, 1920\u20131929 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Repotrectinib in ROS1 fusion\u2013positive non\u2013small-cell lung cancer. N. Engl. J. Med. 390, 118\u2013131 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. NVL-520 is a selective, TRK-sparing, and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations. Cancer Discov. 13, 598\u2013615 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Safety and preliminary clinical activity of NVL-520, a highly selective ROS1 inhibitor, in patients with advanced ROS1 fusion-positive solid tumors. Eur. J. Cancer 174, S6\u2013S7 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. MA06.04 unecritinib in patients with ROS1 positive advanced non-small cell lung cancer: updated results from a phase II trial. J. Thorac. Oncol. 19, S73\u2013S74 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahn, H. K. et al. MET receptor tyrosine kinase regulates the expression of co-stimulatory and co-inhibitory molecules in tumor cells and contributes to PD-L1-mediated suppression of immune cell function. Int. J. Mol. Sci. 20, 4287 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wolf, J. et al. Capmatinib in MET Exon 14\u2013mutated or MET -amplified non\u2013small-cell lung cancer. N. Engl. J. Med. 383, 944\u2013957 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Seto, T. et al. Capmatinib in Japanese patients with MET exon 14 skipping\u2013mutated or MET -amplified advanced NSCLC: GEOMETRY mono-1 study. Cancer Sci. 112, 1556\u20131566 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wolf, J. et al. Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. Lancet Oncol. 25, 1357\u20131370 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mazieres, J. et al. Tepotinib treatment in patients with MET Exon 14\u2013skipping non\u2013small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 9, 1260 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, J.-J. et al. Vebreltinib for advanced non\u2013small cell lung cancer harboring c-met exon 14 skipping mutation: a multicenter, single-arm, phase II KUNPENG study. J. Clin. Oncol. 42, 3680\u20133691 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yu, Y. et al. Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b\/2 trial. eClinicalMedicine 59, 101952 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Long-term efficacy, safety, and subgroup analysis of savolitinib in Chinese patients with NSCLCs harboring MET exon 14 skipping alterations. JTO Clin. Res. Rep. 3, 100407 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xia, Y. et al. Ensartinib for advanced or metastatic non-small-cell lung cancer with MET exon 14 skipping mutations (EMBRACE): a multi-center, single-arm, phase 2 trial. EClinicalMedicine 81, 103099 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat. Med. 26, 47\u201351 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kim, D.-W., Lee, S.-H., Jang, I.-J., Park, K.-J. & Lee, D. H. 998P A phase I study of CKD-702, an EGFR-cMET bispecific antibody, in advanced or metastatic non-small cell lung cancer (NSCLC). Ann. Oncol. 33, S1010 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, B. C. et al. 1173P Early safety, tolerability, and efficacy of REGN5093 in patients (pts) with MET-altered advanced non-small cell lung cancer (aNSCLC) from a first in human (FIH) study. Ann. Oncol. 33, S1085 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Camidge, D. R. et al. Safety and preliminary clinical activity of the MET antibody mixture, Sym015 in advanced non-small cell lung cancer (NSCLC) patients with MET amplification\/exon 14 deletion (METAmp\/Ex14\u2206). J. Clin. Oncol. 38, 9510 (2020).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Remon, J. MET alterations in NSCLC-current perspectives and future challenges. J. Thorac. Oncol. 18, 419\u2013435 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Han, Y. et al. Targeting MET in NSCLC: an ever-expanding territory. JTO Clin. Res. Rep. 5, 100630 (2024).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Guo, R. et al. MET-dependent solid tumours\u2014molecular diagnosis and targeted therapy. Nat. Rev. Clin. Oncol. 17, 569\u2013587 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Camidge, D. R. et al. Crizotinib in patients with MET-amplified NSCLC. J. Thorac. Oncol. 16, 1017\u20131029 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Le, X. et al. Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B. Cell Rep. Med. 4, 101280 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Majeed, U., Manochakian, R., Zhao, Y. & Lou, Y. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J. Hematol. Oncol. 14, 108 (2021).<\/p>\n

Yu, Y. et al. A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib. Ther. Adv. Med. Oncol. 16, 17588359241264730 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Camidge, D. R. et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein\u2013overexpressing advanced nonsquamous EGFR -wildtype non\u2013small cell lung cancer in the phase II LUMINOSITY trial. J. Clin. Oncol. 42, 3000\u20133011 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pereira, F. et al. KRAS as a modulator of the inflammatory tumor microenvironment: therapeutic implications. Cells 11, 398 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sacher, A. et al. Single-agent divarasib (GDC-6036) in solid tumors with a KRAS G12C mutation. N. Engl. J. Med. 389, 710\u2013721 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cui, W. et al. Real world outcomes in KRAS G12C mutation positive non-small cell lung cancer. Lung Cancer 146, 310\u2013317 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dy, G. K. et al. Long-Term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRAS G12C-mutated non\u2013small-cell lung cancer: 2-year analysis of CodeBreaK 100. J. Clin. Oncol. 41, 3311\u20133317 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

de Langen, A. J. et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial. Lancet 401, 733\u2013746 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gadgeel, S. et al. MA06.04 KRYSTAL-1: two-year follow-up of adagrasib (MRTX849) monotherapy in patients with advanced\/metastatic KRASG12C-mutated NSCLC. J. Thorac. Oncol. 18, S118 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Barlesi, F. et al. Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet 406, 615\u2013626 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, Q. et al. Efficacy and safety of KRAS G12C inhibitor IBI351 monotherapy in patients with advanced NSCLC: results from a phase 2 pivotal study. J. Thorac. Oncol. 19, 1630\u20131639 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, Y. et al. Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial. Nat. Med. 31, 894\u2013900 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, Z. et al. Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial. Lancet Respir. Med. 12, 589\u2013598 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhong, J. et al. Sosimerasib monotherapy in patients with previously treated KRAS G12C\u2013mutated non-small cell lung cancer: Primary results of a phase 2 study. J. Clin. Oncol. 43, 8520 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Heist, R. S. et al. Pan-tumor activity of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in patients with KRAS G12C-mutant advanced solid tumors. J. Clin. Oncol. 42, 3007 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, B. T. et al. Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: updated analysis from the international CodeBreaK 101 trial. J. Clin. Oncol. 42, 8512 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Akamatsu, H. et al. A single-arm phase 2 study of sotorasib plus carboplatin and pemetrexed in patients with advanced nonsquamous NSCLC with KRAS G12C mutation (WJOG14821L, SCARLET). J. Thorac. Oncol. 20, 775\u2013785 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Molina-Arcas, M. & Downward, J. Exploiting the therapeutic implications of KRAS inhibition on tumor immunity. Cancer Cell 42, 338\u2013357 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, B. T. et al. OA03.06 CodeBreaK 100\/101: first report of safety\/efficacy of sotorasib in combination with pembrolizumab or atezolizumab in advanced KRAS p.G12C NSCLC. J. Thorac. Oncol. 17, S10\u2013S11 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Janne, P. A. First-line adagrasib (ADA) with pembrolizumab (PEMBRO) in patients (pts) with advanced\/metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) from the phase 2 portion of the KRYSTAL-7 study. J. Clin. Oncol. 43, 8500\u20138500 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dragnev, K. H. et al. Safety and efficacy of olomorasib + immunotherapy in first-line treatment of patients with KRAS G12C-mutant advanced NSCLC: update from the LOXO-RAS-20001 trial. J. Clin. Oncol. 43, 8519 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gregorc, V. et al. KROCUS: a phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC. J. Clin. Oncol. 42, LBA8511 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liermann, J. Cetuximab, gemcitabine and radiotherapy in locally advanced pancreatic cancer: long-term results of the randomized controlled phase II PARC trial. Clin. Transl. Radiat. Oncol. 34, 15\u201322 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, M. et al. Characterization of the treatment-naive immune microenvironment in melanoma with BRAF mutation. J. Immunother. Cancer 10, e004095 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Planchard, D. et al. Phase 2 study of dabrafenib plus trametinib in patients with BRAF V600E-mutant metastatic NSCLC: updated 5-year survival rates and genomic analysis. J. Thorac. Oncol. 17, 103\u2013115 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Planchard, D. et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 17, 984\u2013993 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Planchard, D. et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 18, 1307\u20131316 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Riely, G. J. et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600 -mutant metastatic non\u2013small-cell lung cancer. J. Clin. Oncol. 41, 3700\u20133711 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hyman, D. M. et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N. Engl. J. Med. 373, 726\u2013736 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Subbiah, V. et al. Efficacy of vemurafenib in patients with non\u2013small-cell lung cancer with BRAF V600 mutation: an open-label, single-arm cohort of the histology-independent VE-BASKET study. JCO Precis. Oncol. 3, 1\u20139 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Janku, F. et al. First-in-human study of naporafenib (LXH254) with or without spartalizumab in adult patients with advanced solid tumors harboring MAPK signaling pathway alterations. Eur. J. Cancer 196, 113458 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

McLoughlin, E. M., Fadul, C. E., Patel, S. H., Hall, R. D. & Gentzler, R. D. Clinical and radiographic response of leptomeningeal and brain metastases to encorafenib and binimetinib in a patient with BRAF V600E-mutated lung adenocarcinoma. J. Thorac. Oncol. 14, e269\u2013e271 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Meng, Y. et al. Pralsetinib for the treatment of a RET-positive advanced non-small-cell lung cancer patient harboring both ANK-RET and CCDC6-RET fusions with coronary heart disease: a case report. Ann. Transl. Med. 10, 496\u2013496 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Subbiah, V. et al. Selective RET kinase inhibition for patients with RET-altered cancers. Ann. Oncol. 29, 1869\u20131876 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, W. et al. First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors. Signal Transduct. Target. Ther. 9, 300 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET\u2013rearranged lung cancers. J. Thorac. Oncol. 13, 1595\u20131601 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Griesinger, F. et al. Safety and efficacy of pralsetinib in RET fusion\u2013positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial. Ann. Oncol. 33, 1168\u20131178 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gautschi, O. 35P Final data from phase I\/II LIBRETTO-001 trial of selpercatinib in RET fusion-positive non-small cell lung cancer. ESMO Open 9, 102614 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, C. et al. First-line selpercatinib or chemotherapy and pembrolizumab in RET fusion\u2013positive NSCLC. N. Engl. J. Med. 389, 1839\u20131850 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Subbiah, V. et al. Intracranial efficacy of selpercatinib in RET fusion-positive non\u2013small cell lung cancers on the LIBRETTO-001 trial. Clin. Cancer Res. 27, 4160\u20134167 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tsui, D. C. C. et al. Central nervous system response to selpercartinib in patient with RET-rearranged non-small cell lung cancer after developing leptomeningeal disease on pralsetinib. Clin. Lung Cancer 23, e5\u2013e8 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, Q. et al. A phase I study of KL590586, a next-generation selective RET inhibitor, in patients with RET-altered solid tumors. J. Clin. Oncol. 41, 3007 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Abstract CT201: HS-10365, a highly potent and selective RET tyrosine kinase inhibitor, demonstrates robust activity in RET fusion positive NSCLC patients. Cancer Res. 83, CT201 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Cabozantinib in patients with advanced RET -rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol. 17, 1653\u20131660 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Felip, E. et al. Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: results of the ETOP ALERT-lung trial. Lung Cancer 172, 94\u201399 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Girard, N. et al. Safety and anti-tumor activity of BAY 2927088 in patients with HER2-mutant NSCLC: results from an expansion cohort of the SOHO-01 phase I\/II study. J. Clin. Oncol. 42, LBA8598 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

N\u00fctzinger, J. et al. Management of HER2 alterations in non-small cell lung cancer\u2014the past, present, and future. Lung Cancer 186, 107385 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, X. et al. Novel development strategies and challenges for anti-HER2 antibody-drug conjugates. Antib. Ther. 5, 18\u201329 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fu, Z., Li, S., Han, S., Shi, C. & Zhang, Y. Antibody drug conjugate: the \u201cbiological missile\u201d for targeted cancer therapy. Signal Transduct. Target. Ther. 7, 93 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jacca, S. et al. Bovine herpesvirus 4-based vector delivering a hybrid rat\/human HER-2 oncoantigen efficiently protects mice from autochthonous HER-2+ mammary cancer. OncoImmunology 5, e1082705 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Desai, A., Abdayem, P., Adjei, A. A. & Planchard, D. Antibody-drug conjugates: a promising novel therapeutic approach in lung cancer. Lung Cancer 163, 96\u2013106 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Le, X. et al. Poziotinib in non\u2013small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. J. Clin. Oncol. 40, 710\u2013718 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cornelissen, R. et al. Poziotinib in treatment-naive NSCLC harboring HER2 exon 20 mutations: ZENITH20-4, a multicenter, multicohort, open-label, phase 2 trial (cohort 4). J. Thorac. Oncol. 18, 1031\u20131041 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kris, M. G. et al. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann. Oncol. 26, 1421\u20131427 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, C. et al. Pyrotinib in HER2 -mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study. J. Clin. Oncol. 38, 2753\u20132761 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dziadziuszko, R. et al. Afatinib in NSCLC with HER2 mutations: results of the prospective, open-label phase II NICHE trial of european thoracic oncology platform (ETOP). J. Thorac. Oncol. 14, 1086\u20131094 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Loong, H. H. et al. SOHO-01: safety and efficacy of BAY 2927088 in patients with advanced HER2- mutant non-small cell lung cancer (NSCLC) who were pretreated but na\u00a8\u0131ve to HER2- targeted therapy or had not received any treatment for advanced disease. J. Clin. Oncol. 43, 8504 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Heymach, J. et al. Phase I Beamion Lung 1 trial of BI 1810631, a HER2 tyrosine kinase inhibitor (TKI), as monotherapy in patients (pts) with advanced\/metastatic solid tumors with HER2 aberrations: Updated data. J. Clin. Oncol. 41, 8545 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yamamoto, N. et al. LBA5 Zongertinib in patients with HER2-mutant NSCLC: updated analysis of beamion LUNG-1. Ann. Oncol. 35, S1623\u2013S1624 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mazieres, J. et al. Combination of trastuzumab, pertuzumab, and docetaxel in patients with advanced non\u2013small-cell lung cancer harboring HER2 mutations: results from the IFCT-1703 R2D2 trial. J. Clin. Oncol. 40, 719\u2013728 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

J\u00e4nne, P. A. et al. Final analysis results and patient-reported outcomes from DESTINY-Lung02\u2014a dose-blinded, randomized, phase 2 study of trastuzumab deruxtecan in patients with HER2-mutant metastatic NSCLC. J. Thorac. Oncol. 20, 1814\u20131828 (2025).<\/p>\n

Yang, Y. et al. Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with driver genomic alterations (GA) outside of classic EGFR mutations. J. Clin. Oncol. 43, 3001 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, B. T. et al. Ado-trastuzumab emtansine for patients with HER2 -mutant lung cancers: results from a phase II basket trial. J. Clin. Oncol. 36, 2532\u20132537 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yao, H. et al. Safety, efficacy, and pharmacokinetics of SHR-A1811, a human epidermal growth factor receptor 2\u2013directed antibody-drug conjugate, in human epidermal growth factor receptor 2\u2013expressing or mutated advanced solid tumors: a global phase I trial. J. Clin. Oncol. 42, 3453\u20133465 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Solomon, J. P., Benayed, R., Hechtman, J. F. & Ladanyi, M. Identifying patients with NTRK fusion cancer. Ann. Oncol. 30, viii16\u2013viii22 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Amatu, A. et al. Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer. Ann. Oncol. 30, viii5\u2013viii15 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hong, D. S. et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1\/2 clinical trials. Lancet Oncol. 21, 531\u2013540 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Efficacy of larotrectinib in TRK fusion\u2013positive cancers in adults and children. N. Engl. J. Med. 378, 731\u2013739 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase fusion\u2013positive lung cancers. JCO Precis. Oncol. 6, e2100418 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. E. et al. Long-term efficacy and safety of larotrectinib in patients with TRK fusion lung cancer. J. Clin. Oncol. 42, 8570 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rosen, E. Y. et al. Larotrectinib demonstrates CNS efficacy in TRK fusion-positive solid tumors. JCO Precis. Oncol. 3, PO.19.00009 (2019).<\/p>\n

Doz, F. et al. Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors. Neuro-Oncol. 24, 997\u20131007 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cho, B. C. et al. Updated efficacy and safety of entrectinib in patients (pts) with locally advanced\/metastatic NTRK fusion-positive (fp) non-small cell lung cancer (NSCLC). J. Clin. Oncol. 41, 9047 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Menichincheri, M. et al. Discovery of entrectinib: a new 3-aminoindazole as a potent anaplastic lymphoma kinase (ALK), c-ros oncogene 1 kinase (ROS1), and pan-tropomyosin receptor kinases (Pan-TRKs) inhibitor. J. Med. Chem. 59, 3392\u20133408 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Doebele, R. C. et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1\u20132 trials. Lancet Oncol. 21, 271\u2013282 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Harada, G., Santini, F. C., Wilhelm, C. & Drilon, A. NTRK fusions in lung cancer: from biology to therapy. Lung Cancer 161, 108\u2013113 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Repotrectinib in ROS1 fusion-positive non-small cell lung cancer. N. Engl. J. Med. 390, 118\u2013131 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Roa, P. Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents. Br. J. Cancer 131, 601\u2013610 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. Response to ERBB3-directed targeted therapy in NRG1-rearranged cancers. Cancer Discov. 8, 686\u2013695 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nagasaka, M. & Ou, S.-H. I. Neuregulin 1 fusion\u2013positive NSCLC. J. Thorac. Oncol. 14, 1354\u20131359 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gay, N. D. et al. Durable response to afatinib in lung adenocarcinoma harboring NRG1 gene fusions. J. Thorac. Oncol. 12, e107\u2013e110 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jones, M. R. et al. Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer. Ann. Oncol. 28, 3092\u20133097 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gan, H. K. et al. A phase I, first-in-human study of GSK2849330, an anti-HER3 monoclonal antibody, in HER3-expressing solid tumors. Oncologist 26, e1844\u2013e1853 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schram, A. M. et al. Efficacy of zenocutuzumab in NRG1 fusion\u2013positive cancer. N. Engl. J. Med. 392, 566\u2013576 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hsu, F. et al. EGFR mutation status on brain metastases from non-small cell lung cancer. Lung Cancer 96, 101\u2013107 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Guan, J. et al. EGFR mutations are associated with higher incidence of distant metastases and smaller tumor size in patients with non-small-cell lung cancer based on PET\/CT scan. Med. Oncol. 33, 1 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chen, G. et al. A large, single-center, real-world study of clinicopathological characteristics and treatment in advanced ALK -positive non-small-cell lung cancer. Cancer Med. 6, 953\u2013961 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mendoza, D. P. et al. Imaging features and metastatic patterns of advanced ALK -rearranged non\u2013small cell lung cancer. Am. J. Roentgenol. 214, 766\u2013774 (2020).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, B. et al. JMJD8 promotes malignant progression of lung cancer by maintaining EGFR stability and EGFR\/PI3K\/AKT pathway activation. J. Cancer 12, 976\u2013987 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tsai, M.-F. et al. EGFR-L858R mutant enhances lung adenocarcinoma cell invasive ability and promotes malignant pleural effusion formation through activation of the CXCL12-CXCR4 pathway. Sci. Rep. 5, 13574 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Abdel-Hamid, N. M. & Abass, S. A. Matrix metalloproteinase contribution in management of cancer proliferation, metastasis and drug targeting. Mol. Biol. Rep. 48, 6525\u20136538 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Matuszczak, E. et al. Levels of selected matrix metalloproteinases\u2014MMP-1, MMP-2 and fibronectin in the saliva of patients planned for endodontic treatment or surgical extraction. J. Clin. Med. 9, 3971 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Osude, C. et al. Mediating EGFR-TKI resistance by VEGF\/VEGFR autocrine pathway in non-small cell lung cancer. Cells 11, 1694 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chen, N. et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC: implication for optional immune targeted therapy for NSCLC patients with EGFR mutation. J. Thorac. Oncol. 10, 910\u2013923 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chao, Y.-C. et al. Melatonin downregulates PD-L1 expression and modulates tumor immunity in KRAS-mutant non-small cell lung cancer. Int. J. Mol. Sci. 22, 5649 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kim, S.-J. et al. Alterations in PD-L1 expression associated with acquisition of resistance to ALK Inhibitors in ALK-rearranged lung cancer. Cancer Res. Treat. 51, 1231\u20131240 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tu, E. et al. Anti\u2013PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR-mutated NSCLC. JCI Insight 7, e142843 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Matthews, H. K., Bertoli, C. & De Bruin, R. A. M. Cell cycle control in cancer. Nat. Rev. Mol. Cell Biol. 23, 74\u201388 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cheung, A. H. et al. Out of the cycle: impact of cell cycle aberrations on cancer metabolism and metastasis. Int. J. Cancer 152, 1510\u20131525 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Du, R. et al. TGIF2 promotes the progression of lung adenocarcinoma by bridging EGFR\/RAS\/ERK signaling to cancer cell stemness. Signal Transduct. Target. Ther. 4, 60 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dong, Z.-Y. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. OncoImmunology 6, e1356145 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, A., Wei, T., Meng, H., Luo, P. & Zhang, J. Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. Mol. Cancer 18, 139 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, L. et al. Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma. J. ImmunoTher. Cancer 10, e003534 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hu, L.-Y. EGFR oncogenic mutations in NSCLC impair macrophage phagocytosis and mediate innate immune evasion through up-regulation of CD47. J. Thorac. Oncol. 19, 1186\u20131200 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sereno, M., Hernandez De C\u00f3rdoba, I., Guti\u00e9rrez-Guti\u00e9rrez, G. & Casado, E. Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy. Front. Immunol. 14, 1297988 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tiong, T.-Y. et al. Exosomal miR-21 determines lung-to-brain metastasis specificity through the DGKB\/ERK axis within the tumor microenvironment. Life Sci. 329, 121945 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shih, D. J. H. et al. Genomic characterization of human brain metastases identifies drivers of metastatic lung adenocarcinoma. Nat. Genet. 52, 371\u2013377 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, H. et al. E2F1-mediated repression of WNT5A expression promotes brain metastasis dependent on the ERK1\/2 pathway in EGFR-mutant non-small cell lung cancer. Cell. Mol. Life Sci. 78, 2877\u20132891 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Breindel, J. L. et al. EGF receptor activates MET through MAPK to enhance non\u2013small cell lung carcinoma invasion and brain metastasis. Cancer Res. 73, 5053\u20135065 (2013).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Biswas, A. K. et al. Targeting S100A9\u2013ALDH1A1\u2013retinoic acid signaling to suppress brain relapse in EGFR-mutant lung cancer. Cancer Discov. 12, 1002\u20131021 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Subramaniyan Parimalam, S., Badilescu, S., Sonenberg, N., Bhat, R. & Packirisamy, M. Lab-on-a-chip for the development of pro-\/anti-angiogenic nanomedicines to treat brain diseases. Int. J. Mol. Sci. 20, 6126 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xiao, G. et al. Heterogeneity of tumor immune microenvironment of EGFR\/ALK-positive tumors versus EGFR\/ALK-negative tumors in resected brain metastases from lung adenocarcinoma. J. ImmunoTher. Cancer 11, e006243 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Furugaki, K. et al. Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. Clin. Exp. Metastasis 28, 649\u2013659 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Oh, T.-I. et al. PGC1\u03b1 loss promotes lung cancer metastasis through epithelial-mesenchymal transition. Cancers 13, 1772 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Robichaux, J. P. et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat. Med. 24, 638\u2013646 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, S., Yu, J., Zhang, H. & Liu, J. TP53 co-mutations in advanced EGFR-mutated non\u2013small cell lung cancer: prognosis and therapeutic strategy for cancer therapy. Front. Oncol. 12, 860563 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pao, W. & Chmielecki, J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat. Rev. Cancer 10, 760\u2013774 (2010).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ng, K. P. et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat. Med. 18, 521\u2013528 (2012).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Qin, Q. et al. CDK4\/6 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC). Thorac. Cancer 11, 2389\u20132397 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Volta, F. et al. Intrinsic resistance to osimertinib in EGFR mutated NSCLC cell lines induced by alteration in cell-cycle regulators. Target. Oncol. 18, 953\u2013964 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sharma, G. G. et al. A compound L1196M\/G1202R ALK mutation in a patient with ALK-positive lung cancer with acquired resistance to brigatinib also confers primary resistance to lorlatinib. J. Thorac. Oncol. 14, e257\u2013e259 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, L. et al. Progression patterns, resistant mechanisms and subsequent therapy for ALK-positive NSCLC in the era of second-generation ALK-TKIs. J. Transl. Med. 22, 585 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Siringo, M. Co-Occurrence of ALK rearrangement and KRAS G12C mutation in NSCLC: report of two cases. Curr. Probl. Cancer 14, 100291 (2024).<\/p>\n

Urbanska, E. M. et al. ALK-tyrosine kinase inhibitor intrinsic resistance due to de novo MET-amplification in metastatic ALK-rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination\u2014case report. Transl. Lung Cancer Res. 13, 2453\u20132462 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lara-Mej\u00eda, L. et al. Impact of concurrent genomic alterations on clinical outcomes in patients with ALK-rearranged NSCLC. J. Thorac. Oncol. 19, 119\u2013129 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Drilon, A. et al. ROS1-dependent cancers\u2014biology, diagnostics and therapeutics. Nat. Rev. Clin. Oncol. 18, 35\u201355 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wiesweg, M. et al. High prevalence of concomitant oncogene mutations in prospectively identified patients with ROS1-positive metastatic lung cancer. J. Thorac. Oncol. 12, 54\u201364 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jamme, P. et al. Alterations in the PI3K pathway drive resistance to MET inhibitors in NSCLC harboring MET exon 14 skipping mutations. J. Thorac. Oncol. 15, 741\u2013751 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Suzawa, K. et al. Activation of KRAS mediates resistance to targeted therapy in MET exon 14\u2013mutant non\u2013small cell lung cancer. Clin. Cancer Res. 25, 1248\u20131260 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rotow, J. K. et al. Co-occurring alterations in the RAS-MAPK pathway limit response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer. Clin. Cancer Res. 26, 439\u2013449 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rotow, J. Understanding and targeting resistance mechanisms in NSCLC. Nat. Rev. Cancer 17, 637\u2013658 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, Y. et al. Effective clinical response of lung adenocarcinoma harboring EGFR 19Del\/T790M\/in cis-C797S osimertinib to osimertinib and gefitinib combination therapy. Quant. Imaging Med. Surg. 13, 5362\u20135368 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tan, C.-S. et al. Third generation EGFR TKIs: current data and future directions. Mol. Cancer 17, 29 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nie, L. et al. Nuclear export signal mutation of epidermal growth factor receptor enhances malignant phenotypes of cancer cells. Am. J. Cancer Res. 13, 1209\u20131239 (2023).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sun, Y. et al. Blockade of STAT3\/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization. eBioMedicine 83, 104200 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Passaro, A., J\u00e4nne, P. A., Mok, T. & Peters, S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat. Cancer 2, 377\u2013391 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Starrett, J. H., Guernet, A. A., Cuomo, M. E. & Poels, K. E. Drug sensitivity and allele-specificity of first-line osimertinib resistance EGFR mutations. Cancer Res. 80, 2017\u20132030 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tumbrink, H. L., Heimsoeth, A. & Sos, M. L. The next tier of EGFR resistance mutations in lung cancer. Oncogene 40, 1\u201311 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sequist, L. V. et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 3, 75ra26 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Offin, M. et al. Acquired ALK and RET gene fusions as mechanisms of resistance to osimertinib in EGFR-mutant lung cancers. JCO Precis. Oncol. 2, 1\u201312 (2018).<\/p>\n

Schrock, A. B. et al. Receptor tyrosine kinase fusions and braf kinase fusions are rare but actionable resistance mechanisms to EGFR tyrosine kinase inhibitors. J. Thorac. Oncol. 13, 1312\u20131323 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ou, S.-H. I. et al. Emergence of FGFR3-TACC3 fusions as a potential by-pass resistance mechanism to EGFR tyrosine kinase inhibitors in EGFR mutated NSCLC patients. Lung Cancer 111, 61\u201364 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jakobsen, K. R. et al. MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells. Oncogenesis 6, e307 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, Z. et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat. Genet. 44, 852\u2013860 (2013).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Manabe, T. et al. IGF2 autocrine-mediated IGF1R activation is a clinically relevant mechanism of osimertinib resistance in lung cancer. Mol. Cancer Res. 18, 549\u2013559 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yamaoka, T., Tsurutani, J., Sagara, H. & Ohmori, T. HER2-D16 oncogenic driver mutation confers osimertinib resistance in EGFR mutation-positive non-small cell lung cancer. Transl. Lung Cancer Res. 9, 2178\u20132183 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shi, P. et al. Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment. Cancer Lett. 380, 494\u2013504 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kono, S. A., Marshall, M. E., Ware, K. E. & Heasley, L. E. The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer. Drug Resist. Updates 12, 95\u2013102 (2009).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lee, T.-G. The combination of osimertinib with Raf inhibitor overcomes osimertinib resistance induced by KRAS amplification in EGFR -mutated lung cancer cells. Exp. Cell Res. 430, 113722 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nakatani, K. KRAS and EGFR amplifications mediate resistance to rociletinib and osimertinib in acquired afatinib-resistant NSCLC harboring exon 19 deletion\/T790M in EGFR. Mol. Cancer Ther. 18, 112\u2013126 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sato, H. et al. SRC family kinase inhibition targets YES1 and YAP1 as primary drivers of lung cancer and as mediators of acquired resistance to ALK and epidermal growth factor receptor Inhibitors. JCO Precis. Oncol. 6, e2200088 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nelson, A. W. et al. Novel SPECC1L-MET fusion detected in circulating tumor DNA in a patient with lung adenocarcinoma following treatment with erlotinib and osimertinib. J. Thorac. Oncol. 14, e27\u2013e29 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zeng, L. GOPC-ROS1 rearrangement as an acquired resistance mechanism to osimertinib and responding to crizotinib combined treatments in lung adenocarcinoma. J. Thorac. Oncol. 13, e114\u2013e116 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yoshida, R. et al. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Res. 82, 4079\u20134092 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hsieh, M.-S., Lin, M.-W. & Lee, Y.-H. Lung adenocarcinoma with sarcomatoid transformation after tyrosine kinase inhibitor treatment and chemotherapy. Lung Cancer 137, 76\u201384 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahmad, A. et al. Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs. J. Hematol. Oncol. 6, 77 (2013).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hu, C. et al. LMNA reduced acquired resistance to erlotinib in NSCLC by reversing the epithelial\u2013mesenchymal transition via the FGFR\/MAPK\/c-fos signaling pathway. Int. J. Mol. Sci. 23, 13237 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xu, W. et al. Up-regulation of the Hippo pathway effector TAZ renders lung adenocarcinoma cells harboring EGFR-T790M mutation resistant to gefitinib. Cell Biosci. 5, 7 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xia, G. et al. Transformation of ALK-positive NSCLC to SCLC after alectinib resistance and response to combined atezolizumab: a case report. Transl. Lung Cancer Res. 12, 637\u2013646 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gainor, J. F. et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 6, 1118\u20131133 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Q. Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021. J. Hematol. Oncol. 15, 143 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Poei, D., Ali, S., Ye, S. & Hsu, R. ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies. Cancer Drug Resist. 7, 20 (2024).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Okada, K. et al. Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance. EBioMedicine 41, 105\u2013119 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Recondo, G. et al. Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. Clin. Cancer Res. 26, 242\u2013255 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhu, V. W. et al. A novel sequentially evolved EML4-ALK variant 3 G1202R\/S1206Y double mutation in cis confers resistance to lorlatinib: a brief report and literature review. JTO Clin. Res. Rep. 2, 100116 (2021).<\/p>\n

PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Katayama, R. et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci. Transl. Med. 4, 120ra117 (2012).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pasau, T. et al. Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma. Front. Oncol. 12, 985446 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tabb\u00f2, F., Reale, M. L., Bironzo, P. & Scagliotti, G. V. Resistance to anaplastic lymphoma kinase inhibitors: knowing the enemy is half the battle won. Transl. Lung Cancer Res. 9, 2545\u20132556 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pailler, E. et al. Acquired resistance mutations to ALK inhibitors identified by single circulating tumor cell sequencing in ALK-rearranged non\u2013small-cell lung cancer. Clin. Cancer Res. 25, 6671\u20136682 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

McCoach, C. E. et al. Resistance mechanisms to targeted therapies in ROS1 + and ALK + non\u2013small cell lung cancer. Clin. Cancer Res. 24, 3334\u20133347 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Crystal, A. S. et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 346, 1480\u20131486 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhao, Y., Yang, Y., Xu, Y., Lu, S. & Jian, H. AZD0530 sensitizes drug-resistant ALK-positive lung cancer cells by inhibiting SRC signaling. FEBS Open Bio 7, 472\u2013476 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Levacq, D., D\u2019Haene, N., De Wind, R., Remmelink, M. & Berghmans, T. Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: a new mechanism of resistance to ALK inhibitors. Lung Cancer 102, 38\u201341 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Takegawa, N. et al. Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann. Oncol. 27, 953\u2013955 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Qin, Z. et al. EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation. J. Exp. Med. 221, e20232028 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Caumont, C. et al. Neuroendocrine phenotype as an acquired resistance mechanism in ALK-rearranged lung adenocarcinoma. Lung Cancer 92, 15\u201318 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Shen, J. et al. EML4-ALK G1202R mutation induces EMT and confers resistance to ceritinib in NSCLC cells via activation of STAT3\/Slug signaling. Cell. Signal. 92, 110264 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, Y. et al. EML4-ALK G1202R and EML4-ALK L1196M mutations induce crizotinib resistance in non-small cell lung cancer cells through activating epithelial\u2013mesenchymal transition mediated by MDM2\/MEK\/ERK signal axis. Cell Biol. Int. 49, 55\u201367 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, Q. et al. SIRT1 silencing promotes EMT and Crizotinib resistance by regulating autophagy through AMPK\/mTOR\/S6K signaling pathway in EML4-ALK L1196M and EML4-ALK G1202R mutant non-small cell lung cancer cells. Mol. Carcinog. 63, 2133\u20132144 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, J. J. & Shaw, A. T. Resisting resistance: targeted therapies in lung cancer. Trends Cancer 2, 350\u2013364 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Calabrese, F. et al. Morphologic-molecular transformation of oncogene addicted non-small cell lung cancer. Int. J. Mol. Sci. 23, 4164 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, J. J. et al. Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion\u2013positive lung cancer. Clin. Cancer Res. 27, 2899\u20132909 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Roys, A. et al. Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer. Cancer Chemother. Pharm. 84, 679\u2013688 (2019).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Priest, K. et al. Evolution of acquired resistance in a ROS1+ KRAS G12C+ NSCLC through the MAPK pathway. npj Precis. Oncol 7, 9 (2023).<\/p>\n

CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kondo, N. et al. MIG6 loss confers resistance to ALK\/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF. JCI Insight 8, e173688 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schneider, J. L. et al. Lorlatinib and capmatinib in a ROS1-rearranged NSCLC with MET-driven resistance: tumor response and evolution. npj Precis. Oncol. 7, 116 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, D. et al. Combined lorlatinib, dabrafenib, and trametinib treatment for ROS1-rearranged advanced non-small-cell lung cancer with a lorlatinib-induced BRAF V600E mutation: a case report. Cancer Manag. Res. 14, 3175\u20133179 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dziadziuszko, R. et al. An activating KIT mutation induces crizotinib resistance in ROS1 positive lung cancer. J. Thorac. Oncol. 11, 1273\u20131281 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xu, C. et al. Patient harboring a novel PIK3CA point mutation after acquired resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: a case report and literature review. Thorac. Cancer 8, 714\u2013719 (2017).<\/p>\n

Lin, J. J. Small cell transformation of ROS1 fusion-positive lung cancer resistant to ROS1 inhibition. npj Precis. Oncol 4, 21 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, L. et al. Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer. Proc. Natl. Acad. Sci. 111, E748\u2013E757 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Facchinetti, F. et al. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAFV600E non\u2013small cell lung cancer. Eur. J. Cancer 132, 211\u2013223 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Niemantsverdriet, M. et al. KRAS mutation as a resistance mechanism to BRAF\/MEK Inhibition in NSCLC. J. Thorac. Oncol. 13, e249\u2013e251 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rudin, C. M., Hong, K. & Streit, M. Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small cell lung cancer. J. Thorac. Oncol. 8, e41\u2013e42 (2013).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Abravanel, D. L., Nishino, M., Sholl, L. M., Ambrogio, C. & Awad, M. M. An acquired NRAS Q61K mutation in BRAF V600E-mutant lung adenocarcinoma resistant to dabrafenib plus trametinib. J. Thorac. Oncol. 13, e131\u2013e133 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, V. E. et al. Adaptive resistance to dual BRAF\/MEK inhibition in BRAF-driven tumors through autocrine FGFR pathway activation. Clin. Cancer Res. 25, 7202\u20137217 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yao, Y. et al. Mutations in the MET tyrosine kinase domain and resistance to tyrosine kinase inhibitors in non-small-cell lung cancer. Respir. Res. 24, 28 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bahcall, M. et al. Acquired MET D1228V mutation and resistance to MET inhibition in lung cancer. Cancer Discov. 6, 1334\u20131341 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fujino, T. et al. Sensitivity and resistance of MET exon 14 mutations in lung cancer to eight MET tyrosine kinase inhibitors in vitro. J. Thorac. Oncol. 14, 1753\u20131765 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Recondo, G. et al. Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors in patients with MET exon 14\u2013mutant NSCLC. Clin. Cancer Res. 26, 2615\u20132625 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bahcall, M. et al. Amplification of wild-type KRAS imparts resistance to crizotinib in MET exon 14 mutant non\u2013small cell lung cancer. Clin. Cancer Res. 24, 5963\u20135976 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lin, J. J. et al. Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer. Ann. Oncol. 31, 1725\u20131733 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Solomon, B. J. et al. RET solvent front mutations mediate acquired resistance to selective RET inhibition in RET-driven malignancies. J. Thorac. Oncol. 15, 541\u2013549 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nakaoku, T. A secondary RET mutation in the activation loop conferring resistance to vandetanib. Nat. Commun. 9, 625 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nelson-Taylor, S. K. et al. Resistance to RET-inhibition in RET-rearranged NSCLC is mediated by reactivation of RAS\/MAPK signaling. Mol. Cancer Ther. 16, 1623\u20131633 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Vakkalagadda, C. V. & Patel, J. D. Addition of trastuzumab deruxtecan to selpercatinib in a patient with RET fusion-driven NSCLC and an acquired HER2 amplification: case report. JTO Clin. Res. Rep. 4, 100603 (2023).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Peng, Y. et al. Whole-exome sequencing explored mechanism of selpercatinib resistance in RET-rearranged lung adenocarcinoma transformation into small-cell lung cancer: a case report. BMC Pulm. Med. 23, 492 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gazeu, A. et al. Small-cell lung cancer transformation as a mechanism of resistance to pralsetinib in RET-rearranged lung adenocarcinoma: a case report. Clin. Lung Cancer 24, 72\u201375 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Awad, M. M. et al. Acquired resistance to KRASG12C inhibition in cancer. N. Engl. J. Med. 384, 2382\u20132393 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chour, A., Toffart, A.-C., Berton, E. & Duruisseaux, M. Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer. Front. Oncol. 14, 1328728 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Suzuki, S. et al. KRAS inhibitor resistance in MET-amplified KRAS G12C non\u2013small cell lung cancer induced By RAS- and non\u2013RAS-mediated cell signaling mechanisms. Clin. Cancer Res. 27, 5697\u20135707 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ebi, H. Epithelial to mesenchymal transition is a cause of both intrinsic and acquired resistance to KRAS G12C inhibitor in KRAS G12C mutant non-small cell lung cancer. Clin. Cancer Res. 26, 5962\u20135973 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ryan, M. B. Vertical pathway inhibition overcomes adaptive feedback resistance to KRASG12C inhibition. Clin. Cancer Res. 26, 1633\u20131643 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, F. et al. NTRK fusion in non-small cell lung cancer: diagnosis, therapy, and TRK inhibitor resistance. Front. Oncol. 12, 864666 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schneider, J. L., Lin, J. J. & Shaw, A. T. ALK-positive lung cancer: a moving target. Nat. Cancer 4, 330\u2013343 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

De Jager, V. D., Stigt, J. A., Niemantsverdriet, M., Ter Elst, A. & Van Der Wekken, A. J. Osimertinib and palbociclib in an EGFR-mutated NSCLC with primary CDK4 amplification after progression under osimertinib. npj Precis. Oncol. 8, 113 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Heitzer, E., Haque, I. S., Roberts, C. E. S. & Speicher, M. R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat. Rev. Genet. 20, 71\u201388 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, S.-G. & Shih, J.-Y. Management of acquired resistance to EGFR TKI\u2013targeted therapy in advanced non-small cell lung cancer. Mol. Cancer 17, 38 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Riely, G. J. et al. NCCN Guidelines Index Table of Contents Discussion. (2025). https:\/\/nccn.medlive.cn\/guide\/index<\/a><\/p>\n

Niederst, M. J. et al. The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin. Cancer Res. 21, 3924\u20133933 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b\/2, multicentre, randomised trial. Lancet Respir. Med. 8, 1132\u20131143 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, Y.-L. et al. Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. Lancet Oncol. 25, 989\u20131002 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hartmaier, R. J. et al. Osimertinib + Savolitinib to overcome acquired MET-mediated resistance in epidermal growth factor receptor-mutated, MET-amplified non-small cell lung cancer: TATTON. Cancer Discov. 13, 98\u2013113 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yu, Y. et al. 305MO SCC244 plus osimertinib in patients with stage IIIB\/IIIC or IV, EGFR TKI-resistant EGFR-mutant NSCLC harboring MET amplification. Ann. Oncol. 33, S1553 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahn, M. et al. EP08.02-140 MET biomarker-based preliminary efficacy analysis in SAVANNAH: savolitinib+osimertinib in EGFRm NSCLC post-osimertinib. J. Thorac. Oncol. 17, S469\u2013S470 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Goldman, J. W. et al. Phase 1\/1b study of telisotuzumab vedotin (Teliso-V) + osimertinib (Osi), after failure on prior Osi, in patients with advanced, c-Met overexpressing, EGFR -mutated non-small cell lung cancer (NSCLC). J. Clin. Oncol. 40, 9013 (2022).<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

Camidge, D. R. et al. Phase Ib study of telisotuzumab vedotin in combination with erlotinib in patients with c-met protein\u2013expressing non\u2013small-cell lung cancer. J. Clin. Oncol. 41, 1105\u20131115 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jebbink, M. et al. Trastuzumab-emtansine and osimertinib combination therapy to target HER2 bypass track resistance in EGFR mutation-positive NSCLC. JTO Clin. Res. Rep. 4, 100481 (2023).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wei, X.-W. et al. Characteristics of and treatment strategies for advanced EGFR-mutant NSCLC with concomitant BRAF variations. JTO Clin. Res. Rep. 3, 100348 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zeng, R. et al. EGFR\/BRAF\/MEK co-inhibition for EGFR-mutated lung adenocarcinoma patients with an acquired BRAFV600E mutation: a case report and review of literature. Cancer Drug Resist 4, 1019\u20131027 (2021).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bearz, A., De Carlo, E., Doliana, R. & Schiappacassi, M. Acquired BRAF V600E mutation as resistant mechanism after treatment with third-generation EGFR tyrosine kinase inhibitor. J. Thorac. Oncol. 12, e181\u2013e182 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ernst, S. M. et al. Efficacy and tolerability of osimertinib and sotorasib combination treatment for osimertinib resistance caused by KRAS G12C mutation: a report of two cases. JCO Precis. Oncol. 7, e2300451 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xie, X. et al. Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma. J. Cancer Res. Clin. Oncol. 148, 2165\u20132168 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Qin, Q. et al. Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR -mutant non-small cell lung cancer. Thorac. Cancer 12, 1708\u20131715 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Patel, S. A. et al. IL6 mediates suppression of T- and NK-cell function in EMT-associated TKI-resistant EGFR-mutant NSCLC. Clin. Cancer Res. 29, 1292\u20131304 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mok, T. S. K. et al. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation\u2013positive non\u2013small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J. Clin. Oncol. 35, 4027\u20134034 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Patil, T. et al. Effect of continuing osimertinib with chemotherapy in the post-progression setting on progression-free survival among patients with metastatic epidermal growth factor receptor (EGFR) positive non-small cell lung cancer. J. Clin. Oncol. 39, 9124 (2021).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Watanabe, H. et al. VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers. Cancer Sci. 112, 1853\u20131864 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kawashima, Y. et al. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): Overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir. Med. 10, 72\u201382 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, Q. et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell 39, 1279\u20131291.e3 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Choudhury, N. J., Young, R. J., Sellitti, M., Miller, A. & Drilon, A. Lorlatinib and bevacizumab activity in ALK- rearranged lung cancers after lorlatinib progression. JCO Precis. Oncol. 4, PO-20 (2020).<\/p>\n

Lin, J. J. et al. Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I\/II study. ESMO Open 7, 100342 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Huang, Z. et al. Efficacy and safety of crizotinib plus bevacizumab in ALK\/ROS-1\/c-MET positive non-small cell lung cancer: an open-label, single-arm, prospective observational study. Am. J. Transl. Res. 13, 1526\u20131534 (2021).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wu, T.-C. & Lin, C.-C. Antiangiogenesis may not be a universal booster of EGFR tyrosine kinase inhibitors. J. Thorac. Oncol. 17, 1063\u20131066 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhou, T. et al. Intrathecal chemotherapy combined with systemic therapy in patients with refractory leptomeningeal metastasis of non-small cell lung cancer: a retrospective study. BMC Cancer 23, 333 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lei, T. et al. Anlotinib combined with osimertinib reverses acquired osimertinib resistance in NSCLC by targeting the c-MET\/MYC\/AXL axis. Pharmacol. Res. 188, 106668 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, T. et al. Anlotinib combined with gefitinib can significantly improve the proliferation of epidermal growth factor receptor-mutant advanced non-small cell lung cancer in vitro and in vivo. Transl. Lung Cancer Res. 10, 1873\u20131888 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, S. et al. Role of chemokine-mediated angiogenesis in resistance towards crizotinib and its reversal by anlotinib in EML4-ALK positive NSCLC. J. Transl. Med. 20, 248 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jiang, S. et al. The impact of anlotinib on brain metastases of non-small cell lung cancer: post hoc analysis of a phase III randomized control trial (ALTER0303). Oncologist 25, e870\u2013e874 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chen, L. K. et al. OA03.03 aumolertinib plus anlotinib in advanced NSCLC with brain metastasis: a single-arm, phase II study. J. Thorac. Oncol. 18, S48\u2013S49 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ma, Z. et al. Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography\/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 35, e8955 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, F., Zhu, T., Cao, B., Wang, J. & Liang, L. Apatinib enhances antitumour activity of EGFR-TKIs in non-small cell lung cancer with EGFR-TKI resistance. Eur. J. Cancer 84, 184\u2013192 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, X. et al. Efficacy and safety of combination treatment with apatinib and osimertinib after osimertinib resistance in epidermal growth factor receptor-mutant non-small cell lung carcinoma\u2014a retrospective analysis of a multicenter clinical study. Front. Mol. Biosci. 8, 639892 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nogami, N. et al. IMpower150 final exploratory analyses for atezolizumab plus bevacizumab and chemotherapy in key NSCLC patient subgroups with EGFR mutations or metastases in the liver or brain. J. Thorac. Oncol. 17, 309\u2013323 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bylicki, O. et al. Atezolizumab with or without bevacizumab and platinum-pemetrexed in patients with stage IIIB\/IV non-squamous non-small cell lung cancer with EGFR mutation, ALK rearrangement or ROS1 fusion progressing after targeted therapies: a multicentre phase II open-label non-randomised study GFPC 06-2018. Eur. J. Cancer 183, 38\u201348 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Watanabe, S. et al. A phase II study of atezolizumab with bevacizumab, carboplatin, and paclitaxel for patients with EGFR-mutated NSCLC after TKI treatment failure (NEJ043 study). Eur. J. Cancer 197, 113469 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Park, S. et al. Phase III, randomized study of atezolizumab plus bevacizumab and chemotherapy in patients with EGFR-or ALK-mutated non\u2013small-cell lung cancer (ATTLAS, KCSG-LU19-04). J. Clin. Oncol. 42, 1241\u20131251 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lu, S. et al. Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir. Med. 11, 624\u2013636 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

HARMONi-A Study Investigators et al. Ivonescimab plus chemotherapy in non\u2013small cell lung cancer with EGFR variant: a randomized clinical trial. JAMA 332, 561 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jahanzeb, M. et al. Immunotherapy treatment patterns and outcomes among ALK-positive patients with non\u2013small-cell lung cancer. Clin. Lung Cancer 22, 49\u201357 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gainor, J. F. et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer (NSCLC): a retrospective analysis. Clin. Cancer Res. 22, 4585\u20134593 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mazieres, J. et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann. Oncol. 30, 1321\u20131328 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gadgeel, S. et al. OA09.03 pembrolizumab in combination with platinum-based chemotherapy in recurrent EGFR\/ALK-positive non-small cell lung cancer (NSCLC). J. Thorac. Oncol. 16, S863 (2021).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Guisier, F. et al. Efficacy and safety of anti\u2013PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01-2018. J. Thorac. Oncol. 15, 628\u2013636 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, W. et al. Treatment outcomes and prognosis of patients with primary and acquired BRAF-mutated non-small cell lung cancer: a multicenter retrospective study. Genes Chromosome Canc 61, 530\u2013541 (2022).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu, Z. et al. A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer. Cell 188, 3081\u20133096.e19 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yonesaka, K. HER2-\/HER3-targeting antibody\u2014drug conjugates for treating lung and colorectal cancers resistant to EGFR inhibitors. Cancers 13, 1047 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, L. et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): results from the randomized OptiTROP-Lung03 study. J. Clin. Oncol. 43, 8507 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Le, X. et al. 1O: Osimertinib (osi) + datopotamab deruxtecan (Dato-DXd) in patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC (aNSCLC) whose disease progressed on first-line (1L) osi: ORCHARD. J. Thorac. Oncol. 20, S2\u2013S4 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nadal, E. et al. 124TiP: TROPION-Lung15: a phase III study of datopotamab deruxtecan (dato-DXd) \u00b1 osimertinib vs platinum doublet chemotherapy in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) and disease progression on prior osimertinib. J. Thorac. Oncol. 20, S87\u2013S88 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mok, T. S. K. et al. Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study. J. Clin. Oncol. 43, 8506 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lisberg, A. et al. DB-1310, a HER3-targeted ADC, in pts with advanced solid tumors: preliminary results from the phase 1\/2a trial. J. Clin. Oncol. 43, 3000 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ma, Y. et al. BL-B01D1, a first-in-class EGFR\u2013HER3 bispecific antibody\u2013drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 25, 901\u2013911 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Park, K. et al. Amivantamab in EGFR exon 20 insertion\u2013mutated non\u2013small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J. Clin. Oncol. 39, 3391\u20133402 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Qing, Z. et al. 22P EMB-01: An EGFR-cMET bispecific antibody, in advanced\/metastatic solid tumors phase I results. Ann. Oncol. 33, S39\u2013S40 (2022).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kelly, K. et al. Adjuvant erlotinib versus placebo in patients with stage IB-IIIA non\u2013small-cell lung cancer (RADIANT): a randomized, double-blind, phase III trial. J. Clin. Oncol. 33, 4007\u20134014 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pennell, N. A. et al. SELECT: A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor\u2013mutant non\u2013small-cell lung cancer. J. Clin. Oncol. 37, 97\u2013104 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yue, D. et al. Updated overall survival and exploratory analysis from randomized, phase II EVAN study of erlotinib versus vinorelbine plus cisplatin adjuvant therapy in stage IIIA epidermal growth factor receptor+ non\u2013small-cell lung cancer. J. Clin. Oncol. 40, 3912\u20133917 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yue, D. et al. Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial. Lancet Respir. Med. 6, 863\u2013873 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhong, W.-Z. et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II\u2013IIIA (N1\u2013N2) EGFR-mutant NSCLC (ADJUVANT\/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 19, 139\u2013148 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tada, H. et al. Randomized phase III study of gefitinib versus cisplatin plus vinorelbine for patients with resected stage II-IIIA non\u2013small-cell lung cancer with EGFR mutation (IMPACT). J. Clin. Oncol. 40, 231\u2013241 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

He, J. et al. Icotinib versus chemotherapy as adjuvant treatment for stage II\u2013IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir. Med. 9, 1021\u20131029 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ou, W. et al. Adjuvant icotinib versus observation in patients with completely resected EGFR-mutated stage IB NSCLC (GASTO1003, CORIN): a randomised, open-label, phase 2 trial. eClinicalMedicine 57, 101839 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lv, C. et al. Randomized phase II adjuvant trial to compare two treatment durations of icotinib (2 years versus 1 year) for stage II-IIIA EGFR-positive lung adenocarcinoma patients (ICOMPARE study). ESMO Open 8, 101565 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Li, N. et al. Adjuvant icotinib for resected EGFR-mutated stage II\u2013IIIA non-small-cell lung cancer (ICTAN, GASTO1002): a randomized comparison study. Signal Transduct. Target. Ther. 10, 273 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Herbst, R. S. et al. Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB\u2013IIIA non-small cell lung cancer (NSCLC). J. Clin. Oncol. 41, LBA3 (2023).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cheng, Y. et al. Abstract CT126: aumolertinib as adjuvant therapy in patients with stage II-IIIB EGFR-mutated NSCLC after complete tumor resection: a randomized, double-blind, placebo-controlled, phase 3 trial (ARTS). Cancer Res. 85, CT126 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Han, B. et al. 145P: Efficacy and safety of aumolertinib as adjuvant therapy in resectable stage I A NSCLC with high-risk factors and EGFR-sensitizing mutations (APPOINT). J. Thorac. Oncol. 20, S104\u2013S105 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Neal, J. W. et al. Randomized phase II study of 3 months or 2 years of adjuvant afatinib in patients with surgically resected stage I-III EGFR-mutant non\u2013small-cell lung cancer. JCO Precis. Oncol. 5, 325\u2013332 (2021).<\/p>\n

Zhong, W.-Z. et al. Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR -mutant non\u2013small-cell lung cancer (EMERGING-CTONG 1103): a randomized phase II study. J. Clin. Oncol. 37, 2235\u20132245 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xiong, L. et al. Efficacy of erlotinib as neoadjuvant regimen in EGFR-mutant locally advanced non-small cell lung cancer patients. J. Int. Med. Res. 48, 0300060519887275 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, Y. et al. Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non\u2013small cell lung cancer: a phase II study. J. Thorac. Cardiovasc. Surg. 161, 434\u2013442.e2 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chang, A. E. B. et al. The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC. Oncologist 29, 609\u2013618 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bian, D. et al. Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study. Nat. Commun. 14, 4655 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lv, C. et al. Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): a multicenter, single-arm, open-label phase 2b trial. Lung Cancer 178, 151\u2013156 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Blakely, C. M. et al. Neoadjuvant osimertinib for the treatment of stage I-IIIA epidermal growth factor receptor\u2013mutated non\u2013small cell lung cancer: a phase II multicenter study. J. Clin. Oncol. 42, 3105\u20133114 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

He, J. et al. Neoadjuvant osimertinib for resectable EGFR -mutated non\u2013small cell lung cancer. J. Clin. Oncol. 43, 2875\u20132887 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lee, J. M. P2.01-06 NAUTIKA1 study: preliminary efficacy and safety data with neoadjuvant alectinib in patients with stage IB-III ALK+ NSCLC. J. Thorac. Oncol. 18, S297\u2013S298 (2023).<\/p>\n

Leonetti, A. et al. Alectinib as neoadjuvant treatment in potentially resectable stage III ALK-positive NSCLC: final analysis of ALNEO phase II trial (GOIRC-01-2020-ML42316). J. Clin. Oncol. 43, 8015 (2025).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, C. et al. Induction alectinib or crizotinib for stage III NSCLC harboring ALK fusion: A study with 4-year follow-up. Chin. Med. J. 10, 1097 (2025). Online ahead of print.<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, C. et al. Neoadjuvant crizotinib in resectable locally advanced non\u2013small cell lung cancer with ALK rearrangement. J. Thorac. Oncol. 14, 726\u2013731 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhong, W.-Z. et al. P3.08F.01 interim analysis of a phase 2 prospective trial of induction lorlatinib in locally advanced ALK-positive NSCLC (LORIN). J. Thorac. Oncol. 19, S337\u2013S338 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, G. et al. Neoadjuvant and adjuvant iruplinalkib in resectable ALK or ROS1 fusion-positive, non-small cell lung cancer (NSCLC): the preliminary results of the single-arm, exploratory Neo-INFINITY study. J. Clin. Oncol. 43, e20044 (2025).<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, C. et al. Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: a multicenter pooled analysis. npj Precis. Oncol. 6, 66 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lee, Y. et al. Incorporating erlotinib or irinotecan plus cisplatin into chemoradiotherapy for stage III non-small cell lung cancer according to EGFR mutation status. Cancer Res. Treat. 49, 981\u2013989 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Xing, L. et al. Erlotinib versus etoposide\/cisplatin with radiation therapy in unresectable stage iii epidermal growth factor receptor mutation-positive non-small cell lung cancer: a multicenter, randomized, open-label, phase 2 trial. Int. J. Radiat. Oncol. Biol. Phys. 109, 1349\u20131358 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bi, N. et al. 143P Efficacy and safety of aumolertinib (AUM) with radiotherapy versus concurrent chemoradiotherapy (cCRT) in the treatment of unresectable stage III EGFR-mutant NSCLC: A multicenter, randomized, open-label phase III study (ADVANCE). ESMO Open 9, 102730 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Komaki, R. et al. Adding erlotinib to chemoradiation improves overall survival but not progression-free survival in stage III non-small-cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 92, 317\u2013324 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ramalingam, S. S. et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: Primary results of the phase 3 LAURA study. J. Clin. Oncol. 42, LBA4 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lee, S. Y. et al. P3.08F.06 PLATINUM trial: preliminary analysis of lazertinib therapy in locally advanced, unresectable, EGFR mutation(+) NSCLC following CCRT. J. Thorac. Oncol. 19, S340 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yu, J. et al. PL04.13 aumolertinib maintenance after chemoradiotherapy in stage III non-small-cell lung cancer: interim results of the phase III study (POLESTAR). J. Thorac. Oncol. 19, S6\u2013S7 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Choi, D.-H. et al. Clinical outcomes of maintenance durvalumab after definitive concurrent chemoradiotherapy in unresectable locally advanced stage III non-small cell lung cancer according to epidermal growth factor receptor and anaplastic lymphoma kinase status: Korean Cancer Study Group LU-22-18. J. Clin. Oncol. 42, 8061 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Barsouk, A. et al. Plunging into the PACIFIC: outcomes of patients with unresectable KRAS-mutated non-small cell lung cancer following definitive chemoradiation and durvalumab consolidation. Clin. Lung Cancer 25, e161\u2013e171 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Riudavets, M. et al. Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations. Eur. J. Cancer 167, 142\u2013148 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chiou, G.-Y. et al. Combined stereotactic radiosurgery and tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone for the treatment of non\u2013small cell lung cancer patients with brain metastases. J. Neurosurg. 137, 563\u2013570 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

He, Z.-Y., Li, M.-F., Lin, J.-H., Lin, D. & Lin, R.-J. Comparing the efficacy of concurrent EGFR-TKI and whole-brain radiotherapy vs EGFR-TKI alone as a first-line therapy for advanced EGFR-mutated non-small-cell lung cancer with brain metastases: a retrospective cohort study. Cancer Manag. Res. 11, 2129\u20132138 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ou, S.-H. I. et al. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation. Lung Cancer 96, 15\u201318 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhu, V. W. et al. Symptomatic CNS radiation necrosis requiring neurosurgical resection during treatment with lorlatinib in ALK-rearranged NSCLC: a report of two cases. Lung Cancer Targets Ther. 11, 13\u201318 (2020).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Thomas, N. J. et al. Brain metastases in EGFR- and ALK-positive NSCLC: outcomes of central nervous system-penetrant tyrosine kinase inhibitors alone versus in combination with radiation. J. Thorac. Oncol. 17, 116\u2013129 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Vogelbaum, M. A. et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J. Clin. Oncol. 40, 492\u2013516 (2022).<\/p>\n

Miao, E. et al. Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC). J. Clin. Oncol. 42, 2019 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Arrieta, O. et al. Response rate of patients with baseline brain metastases from recently diagnosed non-small cell lung cancer receiving radiotherapy according to EGFR, ALK and KRAS mutation status. Thorac. Cancer 11, 1026\u20131037 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Johung, K. L. et al. A clinical model for identifying radiosensitive tumor genotypes in non\u2013small cell lung cancer. Clin. Cancer Res. 19, 5523\u20135532 (2013).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Stella, G. M. et al. MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer. Neuro Oncol. 18, 598\u2013599 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yu, H. A. et al. Phase 1 study of twice weekly pulse dose and daily low-dose erlotinib as initial treatment for patients with EGFR-mutant lung cancers. Ann. Oncol. 28, 278\u2013284 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Goldstein, I. M. et al. Dose escalation of osimertinib for intracranial progression in EGFR mutated non-small-cell lung cancer with brain metastases. Neuro-Oncol. Adv. 2, vdaa125 (2020).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zheng, M.-M. et al. Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases. BMC Med. 20, 197 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhao, Y. et al. Co-occurring potentially actionable oncogenic drivers in non-small cell lung cancer. Front. Oncol. 11, 665484 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Peng, D. Effect of EGFR amplification on the prognosis of EGFR-mutated advanced non\u2013small-cell lung cancer patients: a prospective observational study. BMC Cancer 22, 1323 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Blakely, C. M. et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat. Genet. 49, 1693\u20131704 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Skoulidis, F. et al. Co-occurring genomic alterations define major subsets of KRAS -Mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 5, 860\u2013877 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

West, H. J. et al. Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy in KRAS-mutated non-small cell lung cancer with STK11, KEAP1, or TP53 comutations: subgroup results from the phase III IMpower150 trial. J. ImmunoTher. Cancer 10, e003027 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kotecha, R. et al. What drives patient outcomes in brain metastases: number, volume, or biology. J. Clin. Oncol. 35, 2071 (2017).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schneider, J. L. et al. A phase 2 study of lorlatinib in patients with ROS1-rearranged lung cancer with brain-only progression on crizotinib. JTO Clin. Res. Rep. 3, 100347 (2022).<\/p>\n

PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Imyanitov, E. N., Iyevleva, A. G. & Levchenko, E. V. Molecular testing and targeted therapy for non-small cell lung cancer: current status and perspectives. Crit. Rev. Oncol. Hematol. 157, 103194 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pennell, N. A., Arcila, M. E., Gandara, D. R. & West, H. Biomarker testing for patients with advanced non\u2013small cell lung cancer: real-world issues and tough choices. Am. Soc. Clin. Oncol. Educ. Book 39, 531\u2013542 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cohen, D. et al. Optimizing mutation and fusion detection in NSCLC by sequential DNA and RNA sequencing. J. Thorac. Oncol. 15, 1000\u20131014 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhao, Y. et al. Deep learning using histological images for gene mutation prediction in lung cancer: a multicentre retrospective study. Lancet Oncol. 26, 136\u2013146 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dwivedi, K. et al. Enlightening the path to NSCLC biomarkers: utilizing the power of XAI-guided deep learning. Comput. Methods Prog. Biomed. 243, 107864 (2024).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pascual, J. et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann. Oncol. 33, 750\u2013768 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Herbst, R. S. et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB\u2013IIIA non-small-cell lung cancer. Nat. Med. 31, 1958\u20131968 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chaudhuri, A. A., Binkley, M. S., Osmundson, E. C., Alizadeh, A. A. & Diehn, M. Predicting radiotherapy responses and treatment outcomes through analysis of circulating tumor DNA. Semin. Radiat. Oncol. 25, 305\u2013312 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

HHS et al. Use of Circulating Tumor DNA for Curative\u2011Intent Solid Tumor Drug Development \u2013 Guidance for Industry. https:\/\/www.fda.gov\/media\/183874\/download<\/a> (2024).<\/p>\n

Dong, S. et al. Circulating tumor DNA-guided de-escalation targeted therapy for advanced non\u2212small cell lung cancer: a nonrandomized controlled trial. JAMA Oncol. 10, 932 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dong, S. et al. Monitoring of circulating tumor DNA and indication of de-escalation adjuvant targeted therapy for EGFR-mutated NSCLC after complete resection. JTO Clin. Res. Rep. 6, 100758 (2025).<\/p>\n

PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Becker, A. et al. Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur. J. Cancer 47, 2603\u20132606 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Oh, I.-J., Ban, H.-J., Kim, K.-S. & Kim, Y.-C. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer 77, 121\u2013127 (2012).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kuiper, J. L. et al. Rationale and study design of the IRENE-trial (NVALT-16): a phase II trial to evaluate iressa rechallenge in advanced NSCLC patients with an activating EGFR mutation who responded to an EGFR-TKI used as first-line or previous treatment. Clin. Lung Cancer 16, 60\u201366 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ichihara, E. et al. Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. Lung Cancer 132, 54\u201358 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n","protected":false},"excerpt":{"rendered":"Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers…\n","protected":false},"author":2,"featured_media":658905,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[4731,22004,1382,1437,103,61,1704,60,7079,13134,3063,3065],"class_list":["post-658904","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-cancer-research","tag-cancer-therapy","tag-cell-biology","tag-general","tag-health","tag-ie","tag-internal-medicine","tag-ireland","tag-lung-cancer","tag-medicine-public-health","tag-oncology","tag-pathology"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/658904","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=658904"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/658904\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/658905"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=658904"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=658904"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=658904"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}