{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:09:38Z","timestamp":1790730578144,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commissariat G\u00e9n\u00e9ral \u00e0 l\u2019Investissement"},{"name":"Centre National d\u2019Etudes Spatiales (CNES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>While cancer is one of the most documented diseases, how normal cells become cancerous is still debated. To address this question, in the first part of this review, we investigated the long succession of theories of carcinogenesis since antiquity. Initiated by Hippocrates, Aristotle, and Galen, the humoral theory interpreted cancer as an excess of acid, the black bile. The discovery of the circulation of blood by Harvey in 1628 destroyed the basis of the humoral theory but revived the spontaneous generation hypothesis which was also promoted by Aristotle. In 1859, the theory of microbes promoted by Pasteur demonstrated the irrelevance of this last theory and contributed to the emergence of the germ cancer theory, opposed to the cellular theory of cancer, in which cancer was supposed to be caused by microbes or transformed cells, respectively. These theories were progressively refined by the notions of initiation, promotion, and progression thanks to advances in mutagenesis and cellular proliferation. In the second part of this review, recent discoveries and paradigms in carcinogenesis, notably the role of the protein ATM, a major actor of the stress response involved in both mutagenesis and cellular proliferation, were discussed to better understand the current state of the art of carcinogenesis.<\/jats:p>","DOI":"10.3390\/cancers16112104","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:35:32Z","timestamp":1717137332000},"page":"2104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["When DNA Mutations Interplay with Cellular Proliferation: A Narrative History of Theories of Carcinogenesis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-9235","authenticated-orcid":false,"given":"Laura","family":"El Nachef","sequence":"first","affiliation":[{"name":"Inserm U1296 Unit, \u201cRadiation: Defense, Health and Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-8830","authenticated-orcid":false,"given":"Audrey","family":"Bouchet","sequence":"additional","affiliation":[{"name":"Inserm U1296 Unit, \u201cRadiation: Defense, Health and Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-5840","authenticated-orcid":false,"given":"Michel","family":"Bourguignon","sequence":"additional","affiliation":[{"name":"Inserm U1296 Unit, \u201cRadiation: Defense, Health and Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"},{"name":"D\u00e9partement de Biophysique et M\u00e9decine Nucl\u00e9aire, Universit\u00e9 Paris Saclay, Versailles St. Quentin-en-Yvelines, 78035 Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1282-1303","authenticated-orcid":false,"given":"Nicolas","family":"Foray","sequence":"additional","affiliation":[{"name":"Inserm U1296 Unit, \u201cRadiation: Defense, Health and Environment\u201d, 28 Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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