{"id":587051,"date":"2026-04-16T04:13:16","date_gmt":"2026-04-16T04:13:16","guid":{"rendered":"https:\/\/www.newsbeep.com\/us\/587051\/"},"modified":"2026-04-16T04:13:16","modified_gmt":"2026-04-16T04:13:16","slug":"tumour-promotion-through-the-lens-of-evolution","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/us\/587051\/","title":{"rendered":"Tumour promotion through the lens of evolution"},"content":{"rendered":"

Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23\u201328 (1976).<\/p>\n

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

Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).<\/p>\n

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

Bissell, M. J. & Hines, W. C. Why don\u2019t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat. Med. 17, 320\u2013329 (2011).<\/p>\n

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

Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306\u2013313 (2012). This Article noted the significant parallels between clonal selection processes that lead to malignant tumours and the Darwinian processes that shape clonal diversity in response to genetic or environmental influences.<\/p>\n

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

Boveri, T. Zur Frage Der Entstehung Maligner Tumoren (Gustav Fischer, 1914).<\/p>\n

Balmain, A. Peto\u2019s paradox revisited: black box vs mechanistic approaches to understanding the roles of mutations and promoting factors in cancer. Eur. J. Epidemiol. 38, 1251\u20131258 (2023).<\/p>\n

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

Berenblum, I. & Shubik, P. The role of croton oil applications, associated with a single painting of a carcinogen, in tumour induction of the mouse\u2019s skin. Br. J. Cancer 1, 379\u2013382 (1947). This study demonstrated that a single treatment with an established mutagenic carcinogen was sufficient for cancer initiation, when followed by repeated treatment with the tumour-promoting inflammatory agent croton oil, thus establishing the initiation\u2013promotion model of carcinogenesis.<\/p>\n

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

Yuspa, S. H. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis. Cancer Res. 54, 1178\u20131189 (1994).<\/p>\n

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

Slaga, T. J. Overview of tumor promotion in animals. Environ. Health Perspect. 50, 3\u201314 (1983).<\/p>\n

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

Boutwell, R. K., Takigawa, M., Verma, A. K. & Ashendel, C. L. Observations on the mechanism of skin tumor promotion by phorbol esters. Princess Takamatsu Symp. 14, 177\u2013193 (1983).<\/p>\n

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

Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297, 474\u2013478 (1982).<\/p>\n

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

Reddy, E. P., Reynolds, R. K., Santos, E. & Barbacid, M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300, 149\u2013152 (1982).<\/p>\n

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

ICGC International network of cancer genome projects. Nature 464, 993\u2013998 (2010).<\/p>\n

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

Mart\u00ednez-Jim\u00e9nez, F. et al. Pan-cancer whole-genome comparison of primary and metastatic solid tumours. Nature 618, 333\u2013341 (2023).<\/p>\n

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

Campbell, P. J. et al. Pan-cancer analysis of whole genomes. Nature 578, 82\u201393 (2020).<\/p>\n

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

Stratton, M. R., Campbell, P. J. & Futreal, P. A. The cancer genome. Nature 458, 719\u2013724 (2009).<\/p>\n

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

Sabarinathan, R. et al. The whole-genome panorama of cancer drivers. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/190330<\/a> (2017).<\/p>\n

Martincorena, I. et al. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880\u2013886 (2015). This study highlighted the huge mutation burden induced by UV exposure in histologically normal skin, raising the question of why cancers are so rare.<\/p>\n

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

Lawson, A. R. J. et al. Extensive heterogeneity in somatic mutation and selection in the human bladder. Science 370, 75\u201382 (2020).<\/p>\n

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

Mitchell, E. et al. Clonal dynamics of haematopoiesis across the human lifespan. Nature 606, 343\u2013350 (2022).<\/p>\n

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

Lee-Six, H. et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature 574, 532\u2013537 (2019).<\/p>\n

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

Yoshida, K. et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 578, 266\u2013272 (2020).<\/p>\n

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

Abby, E. et al. Notch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth. Nat. Genet. 55, 232\u2013245 (2023).<\/p>\n

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

Lawson, A. R. J. et al. Somatic mutation and selection at population scale. Nature 647, 411\u2013420 (2025).<\/p>\n

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

Calvet, F. et al. Sex and smoking bias in the selection of somatic mutations in human bladder. Nature 647, 436\u2013444 (2025). This was one of the first studies showing the statistical power of somatic mutations detected through ultra-deep sequencing to identify associations between the clonal landscape of normal urothelium and the two most salient bladder cancer risk factors.<\/p>\n

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

Riva, L. et al. The mutational signature profile of known and suspected human carcinogens in mice. Nat. Genet. 52, 1189\u20131197 (2020). In this study, whole genome sequencing of tumours induced in mice by chronic treatment with environmental carcinogens led to the conclusion that most chemical carcinogens have no mutational signature and therefore act as tumour promoters.<\/p>\n

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

Lopez-Bigas, N. & Gonzalez-Perez, A. Are carcinogens direct mutagens? Nat. Genet. 52, 1137\u20131138 (2020).<\/p>\n

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

Moody, S. et al. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence. Nat. Genet. 53, 1553\u20131563 (2021). A search for new mutational signatures indicative of mutagenic exposures as a cause of oesophageal cancers in high-risk countries was proven to be negative, emphasizing the potential role of non-mutagenic carcinogens in human cancer risk.<\/p>\n

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

Senkin, S. et al. Geographic variation of mutagenic exposures in kidney cancer genomes. Nature 629, 910\u2013918 (2024).<\/p>\n

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

D\u00edaz-Gay, M. et al. Geographic and age variations in mutational processes in colorectal cancer. Nature 643, 230\u2013240 (2025).<\/p>\n

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

Dobzhansky, T. Nothing in Biology Makes Sense except in the Light of Evolution. Am. Biol. Teach. 35, 125\u2013129 (1973).<\/p>\n

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

Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020). This landmark study showed the diversity of mutational signatures in human cancers, induced either by environmental mutagens or endogenous processes that control DNA damage and repair.<\/p>\n

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

Gonzalez-Perez, A., Sabarinathan, R. & Lopez-Bigas, N. Local determinants of the mutational landscape of the human genome. Cell 177, 101\u2013114 (2019).<\/p>\n

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

Supek, F. & Lehner, B. Scales and mechanisms of somatic mutation rate variation across the human genome. DNA Repair 81, 102647 (2019).<\/p>\n

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

Stamatoyannopoulos, J. A. et al. Human mutation rate associated with DNA replication timing. Nat. Genet. 41, 393\u2013395 (2009).<\/p>\n

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

Polak, P. et al. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518, 360\u2013364 (2015).<\/p>\n

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

Lawrence, M. S. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214\u2013218 (2013).<\/p>\n

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

Hill, W. et al. Lung adenocarcinoma promotion by air pollutants. Nature 616, 159\u2013167 (2023). This study presents integrated data from a worldwide, multidisciplinary study, encompassing epidemiology, human genetics and mouse lung tumour models, concluding that air pollution contributes to human lung cancer mainly through its activity as a lung tumour promoter.<\/p>\n

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

Hill, W., Weeden, C. E. & Swanton, C. Tumor promoters and opportunities for molecular cancer prevention. Cancer Discov. 14, 1154\u20131160 (2024).<\/p>\n

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

Wynder, E. L. & Hoffmann, D. Some laboratory and epidemiological aspects of air pollution carcinogenesis. J. Air Pollut. Control Assoc. 15, 155\u2013159 (1965).<\/p>\n

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

Clemo, G. R. & Miller, E. W. Tumour promotion by the neutral fraction of cigarette smoke. Br. J. Cancer 14, 651\u2013656 (1960).<\/p>\n

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

Van Duuren, B. L., Sivak, A., Segal, A., Orris, L. & Langseth, L. The tumor-promoting agents of tobacco leaf and tobacco smoke condensate. J. Natl. Cancer Inst. 37, 519\u2013526 (1966). References 40\u201342 drew attention to tumour-promoting effects of tobacco smoking and air pollution, suggesting that some carcinogens can act as both mutagens and tumour promoters.<\/p>\n

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

Alexandrov, L. B. et al. Mutational signatures associated with tobacco smoking in human cancer. Science 354, 618\u2013622 (2016).<\/p>\n

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

Klein, A. M., Brash, D. E., Jones, P. H. & Simons, B. D. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Proc. Natl Acad. Sci. USA 107, 270\u2013275 (2010). This study showed that UV light, a known mutagenic factor, causes clonal expansion by a non-mutagenic process, altering cell fate decisions to promote the outgrowth of p53 mutant cells.<\/p>\n

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

Iversen, O. H. A course of very small doses of DMBA, each of them allegedly with no promoting potency, acts with clear synergistic effect as a strong promoter of DMBA-initiated mouse skin carcinogenesis. A comparison of the tumorigenic and carcinogenic effects of DMBA (7,12-dimethylbenz-alpha-anthracene) and TPA (12-O-tetradecanoyl-phorbol-13-acetate) used as initiators and promoters in classical two-stage experimental protocols. APMIS. Suppl. 41, 1\u201338 (1994).<\/p>\n

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

Ashman, L. K., Murray, A. W., Cook, M. G. & Kotlarski, I. Two-stage skin carcinogenesis in sensitive and resistant mouse strains. Carcinogenesis 3, 99\u2013102 (1982).<\/p>\n

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

Taylor, M. A. et al. Stem-cell states converge in multistage cutaneous squamous cell carcinoma development. Science 384, eadi7453 (2024).<\/p>\n

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

Reeves, M. Q. & Balmain, A. Mutations, bottlenecks, and clonal sweeps: how environmental carcinogens and genomic changes shape clonal evolution during tumor progression. Cold Spring Harb. Perspect. Med. 14, a041388 (2024).<\/p>\n

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

Huang, S. et al. Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. Cell Stem Cell 28, 1582\u20131596.e6 (2021).<\/p>\n

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

Choi, E. et al. Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach. Gut 67, 1595\u20131605 (2018).<\/p>\n

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

Chen, X. et al. IL-17R\u2013EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells. J. Exp. Med. 216, 195\u2013214 (2019).<\/p>\n

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

Morata, G. & Calleja, M. Cell competition and tumorigenesis in the imaginal discs of Drosophila. Semin. Cancer Biol. 63, 19\u201326 (2020).<\/p>\n

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

Nicholson, A. M. et al. Fixation and spread of somatic mutations in adult human colonic epithelium. Cell Stem Cell 22, 909\u2013918.e8 (2018).<\/p>\n

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

Yokoyama, A. et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565, 312\u2013317 (2019).<\/p>\n

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

Fabre, M. A. et al. The longitudinal dynamics and natural history of clonal haematopoiesis. Nature 606, 335\u2013342 (2022).<\/p>\n

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

Mottram, J. C. A developing factor in experimental blastogenesis. J. Pathol. Bacteriol. 56, 181\u2013187 (1944). A landmark study providing evidence that a single treatment with a mutagenic carcinogen was sufficient for cancer initiation, that the initiated cells could lie dormant until exposed to inflammation, and that tissue wounding acts as a strong tumour promoter.<\/p>\n

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

Berenblum, I. The cocarcinogenic action of croton resin. Cancer Res. 1, 44\u201348 (1941).<\/p>\n

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

Berenblum, I. & Shubik, P. The persistence of latent tumour cells induced in the mouse\u2019s skin by a single application of 9:10-dimethyl-1:2-benzanthracene. Br. J. Cancer 3, 384\u2013386 (1949). This work established and extended the concept of initiated cell dormancy originally suggested by Mottram by showing that initiated cells could survive for most of the mouse lifespan without giving rise to tumours, but could give rise to them after short-term exposure to tumour promoters.<\/p>\n

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

Boutwell, R. K., Verma, A. K., Ashendel, C. L. & Astrup, E. Mouse skin: a useful model system for studying the mechanism of chemical carcinogenesis. Carcinog. Compr. Surv. 7, 1\u201312 (1982).<\/p>\n

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

Marks, F., F\u00fcrstenberger, G. & M\u00fcller-Decker, K. in Cancer Prevention. Recent Results in Cancer Research, Vol. 174 (eds Senn, H. J. & Kapp, U.) 37\u201347 (Springer, 2007).<\/p>\n

Hecker, E. Three stage carcinogenesis in mouse skin\u2014recent results and present status of an advanced model system of chemical carcinogenesis. Toxicol. Pathol. 15, 245\u2013258 (1987).<\/p>\n

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

Slaga, T. J. & Butler, A. P. Cellular and biochemical changes during multistage skin tumor promotion. Princess Takamatsu Symp. 14, 291\u2013301 (1983).<\/p>\n

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

Reeves, M. Q., Kandyba, E., Harris, S., Del Rosario, R. & Balmain, A. Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis. Nat. Cell Biol. 20, 699\u2013709 (2018).<\/p>\n

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

McCreery, M. Q. et al. Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat. Med. 21, 1514\u20131520 (2015).<\/p>\n

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

Buqu\u00e9, A. et al. MPA\/DMBA-driven mammary carcinomas. Methods Cell. Biol. 163, 1\u201319 (2021).<\/p>\n

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

Quintanilla, M., Brown, K., Ramsden, M. & Balmain, A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322, 78\u201380 (1986). This work identified a carcinogen-specific signature mutation in over 90% of mouse skin tumours induced by the mutagen DMBA and promoted with the classical tumour promoter TPA, thus identifying the initiating event in the multistage mouse skin model of carcinogenesis.<\/p>\n

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

Goerttler, K., Loehrke, H., Hesse, B., Milz, A. & Schweizer, J. Diaplacental initiation of NMRI mice with 7, 12-dimethylbenz[a]anthracene during gestation days 6\u201320 and postnatal treatment of the F1-generation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate: tumor incidence in organs other than the skin. Carcinogenesis 2, 1087\u20131094 (1981).<\/p>\n

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

Brown, K. et al. v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis. Cell 46, 447\u2013456 (1986).<\/p>\n

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

Li, Y. R. et al. Long-term latency of highly mutated cells in normal mouse skin is reversed by exposure to tumor promoters and chronic tissue damage. Cancer Discov. 15, 1115\u20131128 (2025).<\/p>\n

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

Bailleul, B. et al. Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell 62, 697\u2013708 (1990). References 68\u201370 provided genetic and functional validation of the model of multistage carcinogenesis first proposed in the 1940s, demonstrating that cells with strong cancer driver mutations can lie dormant in mouse skin without causing tumour formation, but respond rapidly to tumour promoters or wounding to produce cancers within a few weeks.<\/p>\n

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

Doll, R. Strategy for detection of cancer hazards to man. Nature 265, 589\u2013596 (1977).<\/p>\n

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

Doll, R. & Peto, R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66, 1191\u20131308 (1981).<\/p>\n

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

Brennan, P. & Davey-Smith, G. Identifying novel causes of cancers to enhance cancer prevention: new strategies are needed. J. Natl. Cancer Inst. 114, 353\u2013360 (2022).<\/p>\n

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

Nordling, C. O. A new theory on cancer-inducing mechanism. Br. J. Cancer 7, 68\u201372 (1953).<\/p>\n

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

Armitage, P. & Doll, R. The age distribution of cancer and a multi-stage theory of carcinogenesis. Br. J. Cancer 8, 1\u201312 (1954). This landmark publication showed the relationship between cancer incidence and age in human populations, identifying a series of 4 to 6 \u2018events\u2019 that could explain age-incidence curves.<\/p>\n

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

Armitage, P. & Doll, R. A two-stage theory of carcinogenesis in relation to the age distribution of human cancer. Br. J. Cancer 11, 161\u2013169 (1957).<\/p>\n

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

Vineis, P. & Berwick, M. The population dynamics of cancer: a Darwinian perspective. Int. J. Epidemiol. 35, 1151\u20131159 (2006).<\/p>\n

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

Peto, R. The need for Ignorance in cancer research. Eur. J. Epidemiol. 38, 1239\u20131243 (2023).<\/p>\n

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

Moolgavkar, S. H., Dewanji, A. & Venzon, D. J. A stochastic two-stage model for cancer risk assessment. I. The hazard function and the probability of tumor. Risk Anal. 8, 383\u2013392 (1988).<\/p>\n

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

Luebeck, E. G. & Moolgavkar, S. H. Multistage carcinogenesis and the incidence of colorectal cancer. Proc. Natl Acad. Sci. USA 99, 15095\u201315100 (2002).<\/p>\n

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

Armitage, P. & Doll, R. in Proc. 4th Berkeley Symposium on Mathematical Statistics and Probability 19\u201338 (Univ. California Press, 1961).<\/p>\n

Sporn, M. B., Dunlop, N. M., Newton, D. L. & Smith, J. M. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed. Proc. 35, 1332\u20131338 (1976).<\/p>\n

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

Sporn, M. B. & Roberts, A. B. Role of retinoids in differentiation and carcinogenesis. Cancer Res. 43, 3034\u20133040 (1983).<\/p>\n

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

Ziegler, R. G. et al. Dietary carotene and vitamin A and risk of lung cancer among white men in New Jersey. J. Natl. Cancer Inst. 73, 1429\u20131435 (1984).<\/p>\n

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

Abar, L. et al. Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF-AICR systematic review of published prospective studies. Cancer Med. 5, 2069\u20132083 (2016).<\/p>\n

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

Omenn, G. S. Chemoprevention of lung cancers: lessons from CARET, the beta-carotene and retinol efficacy trial, and prospects for the future. Eur. J. Cancer Prev. 16, 184 (2007). This study presented an important but sobering lesson from prior attempts at cancer prevention in human populations based on inadequate knowledge of mechanisms of cancer promotion.<\/p>\n

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

Omenn, G. S. et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334, 1150\u20131155 (1996).<\/p>\n

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

Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330, 1029\u20131035 (1994).<\/p>\n

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

Lippman, S. M. et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301, 39\u201351 (2009).<\/p>\n

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

Hennings, H., Wenk, M. L. & Donahoe, R. Retinoic acid promotion of papilloma formation in mouse skin. Cancer Lett. 16, 1\u20135 (1982).<\/p>\n

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

Tennenbaum, T. et al. Topical retinoic acid reduces skin papilloma formation but resistant papillomas are at high risk for malignant conversion. Cancer Res. 58, 1435\u20131443 (1998).<\/p>\n

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

Cui, W. et al. TGF\u03b21 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86, 531\u2013542 (1996).<\/p>\n

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

Perillo, B. et al. ROS in cancer therapy: the bright side of the moon. Exp. Mol. Med. 52, 192\u2013203 (2020).<\/p>\n

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

Sayin, V. I. et al. Antioxidants accelerate lung cancer progression in mice. Sci. Transl. Med. 6, 221ra15 (2014).<\/p>\n

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

Swamynathan, M. M. et al. Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function. Science 386, eadk9167 (2024).<\/p>\n

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

Hecker, E. Cocarcinogenic principles from the seed oil of Croton tiglium and from other Euphorbiaceae. Cancer Res. 28, 2338\u20132349 (1968).<\/p>\n

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

Van Duuren, B. L., Langseth, L., Sivak, A. & Orris, L. The tumor-enhancing principles of Croton tiglium L. II. A comparative study. Cancer Res. 26, 1729\u20131733 (1966). References 96 and 97 described the chemical constituents of croton oil, the original tumour promoter used by Mottram, Berenblum and others, leading to the structural identification and ultimate synthesis of the now classical tumour promoter TPA.<\/p>\n

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

Blumberg, P. M. et al. Phorbol ester receptors-insights into the initial events in the mechanism of action of the phorbol esters. Princess Takamatsu Symp. 14, 75\u201387 (1983).<\/p>\n

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

Castagna, M. et al. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J. Biol. Chem. 257, 7847\u20137851 (1982). Identification of protein kinase C as a direct target of the tumour promoting phorbol ester TPA, enabling many subsequent analyses of the biology of tumour promotion.<\/p>\n

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

Sch\u00f6nwasser, D. C., Marais, R. M., Marshall, C. J. & Parker, P. J. Activation of the mitogen-activated protein kinase\/extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Mol. Cell. Biol. 18, 790\u2013798 (1998).<\/p>\n

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

Nagao, M. et al. Role of protein phosphatases in malignant transformation. Princess Takamatsu Symp. 20, 177\u2013184 (1989).<\/p>\n

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

Suganuma, M. et al. Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc. Natl Acad. Sci. USA 85, 1768\u20131771 (1988). The laboratory of Sugimura identified okadaic acid as a new class of chemical tumour promoter, ultimately shown to act by inhibition of PP2A, thus showing the diversity of tumour-promoting chemicals.<\/p>\n

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

Thastrup, O., Linnebjerg, H., Bjerrum, P. J., Knudsen, J. B. & Christensen, S. B. The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. Biochim. Biophys. Acta 927, 65\u201373 (1987).<\/p>\n

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

Marks, F., F\u00fcrstenberger, G. & Kownatzki, E. Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 41, 696\u2013702 (1981).<\/p>\n

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

Dwyer-Nield, L. D. et al. Epistatic interactions govern chemically-induced lung tumor susceptibility and Kras mutation site in murine C57BL\/6J-ChrA\/J chromosome substitution strains. Int. J. Cancer 126, 125\u2013132 (2010).<\/p>\n

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

Westcott, P. M. K. et al. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer. Nature 517, 489\u2013492 (2015).<\/p>\n

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

Levayer, R. & Moreno, E. Mechanisms of cell competition: themes and variations. J. Cell Biol. 200, 689\u2013698 (2013).<\/p>\n

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

Aydinlik, H., Nguyen, T. D., Moennikes, O., Buchmann, A. & Schwarz, M. Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors. Oncogene 20, 7812\u20137816 (2001).<\/p>\n

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

Witherspoon, J. G. et al. Mutant Nrf2E79Q enhances the promotion and progression of a subset of oncogenic Ras keratinocytes and skin tumors. Redox Biol. 75, 103261 (2024).<\/p>\n

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

Baggiolini, A. et al. Developmental chromatin programs determine oncogenic competence in melanoma. Science 373, eabc1048 (2021).<\/p>\n

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

Lapouge, G. et al. Identifying the cellular origin of squamous skin tumors. Proc. Natl Acad. Sci. USA 108, 7431\u20137436 (2011).<\/p>\n

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

Brown, K., Strathdee, D., Bryson, S., Lambie, W. & Balmain, A. The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted. Curr. Biol. 8, 516\u2013524 (1998).<\/p>\n

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

Su, F. et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N. Engl. J. Med. 366, 207\u2013215 (2012).<\/p>\n

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

Yang, Y. et al. The pioneer factor SOX9 competes for epigenetic factors to switch stem cell fates. Nat. Cell Biol. 25, 1185\u20131195 (2023).<\/p>\n

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

Sorg, B., F\u00fcrstenberger, G., Berry, D. L., Hecker, E. & Marks, F. Preparation of retinoic acid esters of phorbol derivatives. J. Lipid Res. 23, 443\u2013447 (1982).<\/p>\n

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

Akhurst, R. J., Fee, F. & Balmain, A. Localized production of TGF-\u03b2 mRNA in tumour promoter-stimulated mouse epidermis. Nature 331, 363\u2013365 (1988). This work demonstrated that the tumour promoter TPA induces activation of the TGF\u03b2 signalling pathway, subsequently shown to be important in growth control, invasion, immunosuppression, and tumour progression.<\/p>\n

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

Glick, A. B. & Yuspa, S. H. Tissue homeostasis and the control of the neoplastic phenotype in epithelial cancers. Semin. Cancer Biol. 15, 75\u201383 (2005).<\/p>\n

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

Trosko, J. E. & Ruch, R. J. Gap junctions as targets for cancer chemoprevention and chemotherapy. Curr. Drug Targets 3, 465\u2013482 (2002).<\/p>\n

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

MacCarthy-Morrogh, L. & Martin, P. The hallmarks of cancer are also the hallmarks of wound healing. Sci. Signal. 13, eaay8690 (2020).<\/p>\n

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

Brown, L. M., Malkinson, A. M., Rannels, D. E. & Rannels, S. R. Compensatory lung growth after partial pneumonectomy enhances lung tumorigenesis induced by 3-methylcholanthrene. Cancer Res. 59, 5089\u20135092 (1999).<\/p>\n

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

Argyris, T. S. Regeneration and the mechanism of epidermal tumor promotion. Crit. Rev. Toxicol. 14, 211\u2013258 (1985).<\/p>\n

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

Pitot, H. C. The natural history of neoplasia. Newer insights into an old problem. Am. J. Pathol. 89, 402\u2013411 (1977).<\/p>\n

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

Mangiante, L. et al. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity. Nat. Genet. 55, 607\u2013618 (2023).<\/p>\n

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

Rubin, H. Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis. Oncogene 21, 7392\u20137411 (2002).<\/p>\n

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

Chen, Y. et al. Consumption of hot beverages and foods and the risk of esophageal cancer: a meta-analysis of observational studies. BMC Cancer 15, 449 (2015).<\/p>\n

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

Rapozo, D. C. M. et al. Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus. Exp. Mol. Pathol. 100, 325\u2013331 (2016).<\/p>\n

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

Berrington de Gonz\u00e1lez, A. et al. Advisory Group recommendations on priorities for the IARC Monographs. Lancet Oncol. 25, 546\u2013548 (2024).<\/p>\n

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

Bolton, K. L. et al. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat. Genet. 52, 1219\u20131226 (2020).<\/p>\n

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

Pich, O., Reyes-Salazar, I., Gonzalez-Perez, A. & Lopez-Bigas, N. Discovering the drivers of clonal hematopoiesis. Nat. Commun. 13, 4267 (2022).<\/p>\n

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

Hagiwara, K. et al. Dynamics of age- versus therapy-related clonal hematopoiesis in long-term survivors of pediatric cancer. Cancer Discov. 13, 844\u2013857 (2023).<\/p>\n

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

Moore, T., Beltran, L., Carbajal, S., Hursting, S. D. & DiGiovanni, J. Energy balance modulates mouse skin tumor promotion through altered IGF-1R and EGFR crosstalk. Cancer Prev. Res. 5, 1236\u20131246 (2012).<\/p>\n

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

Halliwill, K. D. et al. Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer. Genome Med. 8, 83 (2016).<\/p>\n

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

Kurz, E. et al. Exercise-induced engagement of the IL-15\/IL-15R\u03b1 axis promotes anti-tumor immunity in pancreatic cancer. Cancer Cell 40, 720\u2013737.e5 (2022).<\/p>\n

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

Ding, R. et al. Size-dependent toxicity of polystyrene microplastics on the gastrointestinal tract: oxidative stress related-DNA damage and potential carcinogenicity. Sci. Total Environ. 912, 169514 (2024).<\/p>\n

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

Zahm, S. et al. Carcinogenicity of perfluorooctanoic acid and perfluorooctanesulfonic acid. Lancet Oncol. 25, 16\u201317 (2024).<\/p>\n

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

Tommasi, S. et al. Deregulation of biologically significant genes and associated molecular pathways in the oral epithelium of electronic cigarette users. Int. J. Mol. Sci. 20, 738 (2019).<\/p>\n

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

Tang, M.-S. et al. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc. Natl Acad. Sci. USA 116, 21727\u201321731 (2019).<\/p>\n

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

Uemura, N. et al. Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 345, 784\u2013789 (2001).<\/p>\n

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

Ushijima, T. & Hattori, N. Molecular pathways: involvement of Helicobacter pylori-triggered inflammation in the formation of an epigenetic field defect, and its usefulness as cancer risk and exposure markers. Clin. Cancer Res. 18, 923\u2013929 (2012).<\/p>\n

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

Pleguezuelos-Manzano, C. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269\u2013273 (2020).<\/p>\n

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

O\u2019Dowd, A. GLP-1 receptor agonists: MHRA to study possible side effects after acute pancreatitis cases. Brit. Med. J. 389, r1344 (2025).<\/p>\n

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

Braxton, A. M. et al. 3D genomic mapping reveals multifocality of human pancreatic precancers. Nature 629, 679\u2013687 (2024). This study provides a graphic demonstration of the presence of PANINs harbouring strong oncogenic KRAS mutations in normal human pancreas samples across a wide range of patient ages, supporting the view that promoter-induced activation of inflammation and pancreatitis may be a rate-limiting step in development of pancreatic cancers.<\/p>\n

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

Ames, B. N., Durston, W. E., Yamasaki, E. & Lee, F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl Acad. Sci. USA 70, 2281\u20132285 (1973).<\/p>\n

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

Kennedy, S. R. et al. Detecting ultralow-frequency mutations by duplex sequencing. Nat. Protoc. 9, 2586\u20132606 (2014).<\/p>\n

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

Abascal, F. et al. Somatic mutation landscapes at single-molecule resolution. Nature 593, 405\u2013410 (2021).<\/p>\n

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

Valentine, C. C. et al. Direct quantification of in vivo mutagenesis and carcinogenesis using duplex sequencing. Proc. Natl Acad. Sci. USA 117, 33414\u201333425 (2020).<\/p>\n

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

Yokoyama, A. et al. Somatic mosaicism in the buccal mucosa reflects lifestyle and germline risk factors for esophageal squamous cell carcinoma. Sci. Transl. Med. 17, eadq6740 (2025).<\/p>\n

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

Grundberg, I. et al. In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics. Oncotarget 4, 2407\u20132418 (2013).<\/p>\n

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

Torrens, L. et al. The complexity of tobacco smoke-induced mutagenesis in head and neck cancer. Nat. Genet. 57, 884\u2013896 (2025).<\/p>\n

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

Sudlow, C. et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).<\/p>\n

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

Sun, B. B. et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622, 329\u2013338 (2023).<\/p>\n

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

Wang, X. et al. A pathology foundation model for cancer diagnosis and prognosis prediction. Nature 634, 970\u2013978 (2024).<\/p>\n

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

Flanagan, D. J. et al. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature 594, 430\u2013435 (2021).<\/p>\n

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

van Neerven, S. M. et al. Apc-mutant cells act as supercompetitors in intestinal tumour initiation. Nature 594, 436\u2013441 (2021).<\/p>\n

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

Slaga, T. J. Sivak, A. & Boutwell, R. K. (eds) Mechanisms of Tumor Promotion and Cocarcinogenesis (Raven Press, 1978).<\/p>\n

Slaga, T. J. (ed.) Tumor Promotion in Internal Organs (CRC Press, 1983).<\/p>\n

George, J., Prasad, S., Mahmood, Z. & Shukla, Y. Studies on glyphosate-induced carcinogenicity in mouse skin: a proteomic approach. J. Proteomics 73, 951\u2013964 (2010).<\/p>\n

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

Bauer, A. K., Dwyer-Nield, L. D., Keil, K., Koski, K. & Malkinson, A. M. Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: a role in tumor promotion. Exp. Lung Res. 27, 197\u2013216 (2001).<\/p>\n

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

Guerra, C. et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11, 291\u2013302 (2007).<\/p>\n

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

Liang, C. et al. Orthotopic inflammation-related pancreatic carcinogenesis in a wild-type mouse induced by combined application of caerulein and dimethylbenzanthracene. Tumour Biol. 36, 7557\u20137568 (2015).<\/p>\n

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

Tanaka, T. et al. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci. 94, 965\u2013973 (2003).<\/p>\n

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

Braeuning, A. et al. Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice. Arch. Toxicol. 90, 1481\u20131494 (2016).<\/p>\n

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

Poland, A., Palen, D. & Glover, E. Tumour promotion by TCDD in skin of HRS\/J hairless mice. Nature 300, 271\u2013273 (1982).<\/p>\n

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

Luebeck, E. G., Buchmann, A., Stinchcombe, S., Moolgavkar, S. H. & Schwarz, M. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on initiation and promotion of GST-P-positive foci in rat liver: A quantitative analysis of experimental data using a stochastic model. Toxicol. Appl. Pharmacol. 167, 63\u201373 (2000).<\/p>\n

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

D\u2019Orazio, J., Jarrett, S., Amaro-Ortiz, A. & Scott, T. UV radiation and the skin. Int. J. Mol. Sci. 14, 12222\u201312248 (2013).<\/p>\n

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

Cohen, A. J. et al. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet 389, 1907\u20131918 (2017).<\/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. Particulate matter air pollution as a cause of lung cancer: epidemiological and experimental evidence. Br. J. Cancer 132, 986\u2013996 (2025).<\/p>\n

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

Das, A. The emerging role of microplastics in systemic toxicity: Involvement of reactive oxygen species (ROS). Sci. Total Environ. 895, 165076 (2023).<\/p>\n

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

Omoike, O. E. et al. Association between per and polyfluoroalkyl substances and markers of inflammation and oxidative stress. Environ. Res. 196, 110361 (2021).<\/p>\n

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

Shane, H. L., Baur, R., Lukomska, E., Weatherly, L. & Anderson, S. E. Immunotoxicity and allergenic potential induced by topical application of perfluorooctanoic acid (PFOA) in a murine model. Food Chem. Toxicol. 136, 111114 (2020).<\/p>\n

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

Seyyedsalehi, M. S. & Boffetta, P. Per- and poly-fluoroalkyl substances (PFAS) exposure and risk of kidney, liver, and testicular cancers. Med. Lav. 114, e2023040 (2023).<\/p>\n

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

Alpert, N., van Gerwen, M. & Taioli, E. Epidemiology of mesothelioma in the 21st century in Europe and the United States, 40 years after restricted\/banned asbestos use. Transl. Lung Cancer Res. 9, S28\u2013S38 (2020).<\/p>\n

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

Eriksson, M., Hardell, L., Carlberg, M. & Akerman, M. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis. Int. J. Cancer 123, 1657\u20131663 (2008).<\/p>\n

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

Chen, D. et al. Childhood and adolescent residential and farm pesticide exposures and inflammatory bowel disease incidence in a U.S. cohort of women. Sci. Total Environ. 946, 174475 (2024).<\/p>\n

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

Schinasi, L. & Leon, M. E. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int. J. Environ. Res. Public. Health 11, 4449\u20134527 (2014).<\/p>\n

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

Kielhorn, J., Melber, C., Wahnschaffe, U., Aitio, A. & Mangelsdorf, I. Vinyl chloride: still a cause for concern. Environ. Health Perspect. 108, 579\u2013588 (2000).<\/p>\n

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

Yang, X., Du, J., Jia, C., Yang, T. & Shao, S. Groundwater pollution risk, health effects and sustainable management of halocarbons in typical industrial parks. Environ. Res. 250, 118422 (2024).<\/p>\n

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

Leja, M. Where are we with gastric cancer screening in Europe in 2024? Gut 73, 2074\u20132082 (2024).<\/p>\n

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

Cornish, A. J. et al. The genomic landscape of 2,023 colorectal cancers. Nature 633, 127\u2013136 (2024).<\/p>\n

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

Cohen, P. A., Jhingran, A., Oaknin, A. & Denny, L. Cervical cancer. Lancet 393, 169\u2013182 (2019).<\/p>\n

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

Capasso, M., Cossiga, V., Guarino, M., Ranieri, L. & Morisco, F. The role of hepatitis viruses as drivers of hepatocancerogenesis. Cancers 16, 1505 (2024).<\/p>\n

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

Roe, F. J., Salaman, M. H. & Cohen, J. Incomplete carcinogens in cigarette smoke condensate: tumour-promotion by a phenolic fraction. Br. J. Cancer 13, 623\u2013633 (1959).<\/p>\n

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

Glantz, S. A., Nguyen, N. & Oliveira da Silva, A. L. Population-based disease odds for e-cigarettes and dual use versus cigarettes. NEJM Evid. 3, EVIDoa2300229 (2024).<\/p>\n

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

Kinouchi, K. & Sassone-Corsi, P. Metabolic rivalry: circadian homeostasis and tumorigenesis. Nat. Rev. Cancer 20, 645\u2013661 (2020).<\/p>\n

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

Costa, G. [Shift work and breast cancer]. G. Ital. Med. Lav. Ergon. 32, 454\u2013457 (2010).<\/p>\n

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

Rumgay, H. et al. Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol. 22, 1071\u20131080 (2021).<\/p>\n

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

Bagnardi, V. et al. Light alcohol drinking and cancer: a meta-analysis. Ann. Oncol. 24, 301\u2013308 (2013).<\/p>\n

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

Scoccianti, C. et al. European Code against Cancer 4th Edition: alcohol drinking and cancer. Cancer Epidemiol. 45, 181\u2013188 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n","protected":false},"excerpt":{"rendered":"Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23\u201328 (1976). Article\u00a0 CAS\u00a0 PubMed\u00a0 ADS\u00a0…\n","protected":false},"author":2,"featured_media":587052,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[74787,31773,70007,97,1159,1160,14296,79],"class_list":{"0":"post-587051","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-cancer-models","9":"tag-cancer-prevention","10":"tag-evolutionary-genetics","11":"tag-health","12":"tag-humanities-and-social-sciences","13":"tag-multidisciplinary","14":"tag-risk-factors","15":"tag-science"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/587051","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/comments?post=587051"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/587051\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media\/587052"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media?parent=587051"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/categories?post=587051"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/tags?post=587051"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}