Kaufman, B. et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J. Clin. Oncol. 33, 244–250 (2015).
Mirza, M. R. et al. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol. Oncol. 159, 442–448 (2020).
Coleman, R. L. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390, 1949–1961 (2017).
Kristeleit, R. et al. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin. Cancer Res. 23, 4095–4106 (2017).
Swisher, E. M. et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 18, 75–87 (2017).
Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).
Laspata, N. et al. PARP1 associates with R-loops to promote their resolution and genome stability. Nucleic Acids Res. 51, 2215–2237 (2023).
Murai, J. et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res 72, 5588–5599 (2012).
Ribeiro, J. et al. Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells. Nucleic Acids Res. 53, gkaf1398 (2025).
Ying, S., Hamdy, F. C. & Helleday, T. Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. Cancer Res 72, 2814–2821 (2012).
Panzarino, N. J. et al. Replication gaps underlie BRCA deficiency and therapy response. Cancer Res. 81, 1388–1397 (2021).
Petropoulos, M. et al. Transcription-replication conflicts underlie sensitivity to PARP inhibitors. Nature 628, 433–441 (2024).
Taylor, R. C., Cullen, S. P. & Martin, S. J. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9, 231–241 (2008).
Yuan, J. & Ofengeim, D. A guide to cell death pathways. Nat. Rev. Mol. Cell Biol. 25, 379–395 (2024).
Newton, K., Strasser, A., Kayagaki, N. & Dixit, V. M. Cell death. Cell 187, 235–256 (2024).
Croce, C. M. et al. The BCL-2 protein family: from discovery to drug development. Cell Death Differ. 32, 1369–1381 (2025).
Fleury, H. et al. Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence. Nat. Commun. 10, 2556 (2019).
Wyld, L. et al. Senescence and cancer: a review of clinical implications of senescence and senotherapies. Cancers (Basel) 12, 2134 (2020).
de Magalhaes, J. P. Cellular senescence in normal physiology. Science 384, 1300–1301 (2024).
Achuthan, S., Santhoshkumar, T. R., Prabhakar, J., Nair, S. A. & Pillai, M. R. Drug-induced senescence generates chemoresistant stemlike cells with low reactive oxygen species. J. Biol. Chem. 286, 37813–37829 (2011).
Paffenholz, S. V. et al. Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer. Proc. Natl. Acad. Sci. USA 119, e2117754119 (2022).
Zhang, S. et al. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene 33, 116–128 (2014).
Harrington B. S., Annunziata C. M. NF-kappaB signaling in ovarian cancer. Cancers (Basel) 11, 1182 (2019).
Diepstraten, S. T. et al. The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs. Nat. Rev. Cancer 22, 45–64 (2022).
Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899–905 (2010).
Vogler, M. Targeting BCL2-proteins for the treatment of solid tumours. Adv. Med. 2014, 943648 (2014).
Li, M., Wang, D., He, J., Chen, L. & Li, H. Bcl-X(L): a multifunctional anti-apoptotic protein. Pharmacol. Res. 151, 104547 (2020).
Dai, H., Meng, X. W. & Kaufmann, S. H. Mitochondrial apoptosis and BH3 mimetics. F1000Res 5, 2804 (2016).
Stover, E. H. et al. Pooled genomic screens identify anti-apoptotic genes as targetable mediators of chemotherapy resistance in ovarian cancer. Mol. Cancer Res. 17, 2281–2293 (2019).
Liu, D. et al. Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer. Cell Death Dis. 12, 789 (2021).
Yosef, R. et al. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat. Commun. 7, 11190 (2016).
Witham, J. et al. The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to carboplatin. Clin. Cancer Res. 13, 7191–7198 (2007).
Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016).
Bharti, V. et al. BCL-xL inhibition potentiates cancer therapies by redirecting the outcome of p53 activation from senescence to apoptosis. Cell Rep. 41, 111826 (2022).
Hurley, R. M. et al. Characterization of a RAD51C-silenced high grade serous ovarian cancer model during development of PARP inhibitor resistance. NAR Cancer 3, zcab028 (2021).
Zhang, X. et al. Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer. Sci. Adv. 9, eadf7195 (2023).
Fong, P. C. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123–134 (2009).
Martin, S. J. et al. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med 182, 1545–1556 (1995).
Lee, S. H., Meng, X. W., Flatten, K. S., Loegering, D. A. & Kaufmann, S. H. Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking between plasma membrane and cytoplasm. Cell Death Differ. 20, 64–76 (2013).
Kortmann, U. et al. Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived ovarian cancer tissue xenografts. Clin. Cancer Res. 17, 783–791 (2011).
Patel, A. G., De Lorenzo, S. B., Flatten, K. S., Poirier, G. G. & Kaufmann, S. H. Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin. Cancer Res. 18, 1655–1662 (2012).
Goto, H. et al. Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J. Biol. Chem. 274, 25543–25549 (1999).
Sakai, W. et al. Functional restoration of BRCA2 protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma. Cancer Res 69, 6381–6386 (2009).
McGehee, C. D. et al. Codon specific readthrough as a mechanism of BRCA2 restoration in acquired PARP inhibitor and chemotherapy resistance. Nucleic Acids Res. 53, gkaf990 (2025).
Antolin, A. A. et al. The kinase polypharmacology landscape of clinical PARP inhibitors. Sci. Rep. 10, 2585 (2020).
Knezevic, C. E. et al. Proteome-wide profiling of clinical PARP inhibitors reveals compound-specific secondary targets. Cell Chem. Biol. 23, 1490–1503 (2016).
Cardenas, C. et al. Adipocyte microenvironment promotes Bcl(xl) expression and confers chemoresistance in ovarian cancer cells. Apoptosis 22, 558–569 (2017).
Venkatachalam, A. et al. Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors. Mol. Cancer 23, 224 (2024).
da Costa, A., Chowdhury, D., Shapiro, G. I., D’Andrea, A. D., Konstantinopoulos, P. A. Targeting replication stress in cancer therapy. Nat. Rev. Drug Discov. 22, 38–58 (2022).
Leverson, J. D. et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci. Transl. Med. 7, 279ra240 (2015).
Al, H. illiM. M. et al. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma. Gynecol. Oncol. 143, 379–388 (2016).
DiSilvestro, P. et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. J. Clin. Oncol. 41, 609–617 (2023).
Monk, B. J. et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann. Oncol. 35, 981–992 (2024).
Cecere, S. C. et al. Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: real world data and post progression outcome. Gynecol. Oncol. 156, 38–44 (2020).
Hurley, R. M. et al. 53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer. Gynecol. Oncol. 153, 127–134 (2019).
Lord, C. J. & Ashworth, A. PARP inhibitors: Synthetic lethality in the clinic. Science 355, 1152–1158 (2017).
Lheureux, S. et al. EVOLVE: A multicenter open-label single-arm clinical and translational phase II Trial of cediranib plus olaparib for ovarian cancer after PARP inhibition progression. Clin. Cancer Res. 26, 4206–4215 (2020).
Swisher, E. M. et al. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). Nat. Commun. 12, 2487 (2021).
Collet, L. et al. BRCA1/2 alterations and reversion mutations in the area of PARP inhibitors in high grade ovarian cancer: state of the art and forthcoming challenges. Front Oncol. 14, 1354427 (2024).
Puthalakath, H., Huang, D. C. S., O’Reilly, L. A., King, S. M. & Strasser, A. The proapoptotic activity of the Bcl-2 family member bim is regulated by interaction with the dynein motor complex. Mol. Cell 3, 287–296 (1999).
Montero, J. et al. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell 160, 977–989 (2015).
Rodman, E. P. B. et al. Lestaurtinib’s antineoplastic activity converges on JAK/STAT signaling to inhibit treatment naive and therapy resistant forms ovarian cancer. npj Precis. Oncol. 9, 236 (2025).
Kaufmann, S. H. et al. Altered Formation of Topotecan-Stabilized Topoisomerase I-DNA Adducts in Human Leukemia Cells. Blood 89, 2098–2104 (1997).
Kaufmann, S. H. Reutilization of Immunoblots After Chemiluminescent Detection. Anal. Biochem 296, 283–286 (2001).
Dai, H. et al. Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells. Genes Dev. 29, 2140–2152 (2015).
Cliby, W. A., Lewis, K. A., Lilly, K. K. & Kaufmann, S. H. S phase and G2 arrests induced by topoisomerase I poisons are dependent on ATR kinase function. J. Biol. Chem. 277, 1599–1606 (2002).
Chou, T.-C. & Talalay, P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzym. Reg. 22, 27–55 (1984).
Berenbaum, M. C. What is Synergy? Pharmacol. Rev. 41, 93–141 (1989).
Weroha, S. J. et al. Tumorgrafts as in vivo surrogates for women with ovarian cancer. Clin. Cancer Res. 20, 1288–1297 (2014).
Oberg, A. L. et al. Statistical analysis of comparative tumor growth repeated measures experiments in the ovarian cancer patient derived xenograft (PDX) setting. Sci. Rep. 11, 8076 (2021).