Catania F. auteur aut IRD Ujvari B. auteur aut IRD Roche Benjamin auteur aut IRD Capp J. P. auteur aut IRD Thomas F. auteur aut IRD text journalArticle eng text/pdf reformatted digital access Although neo-Darwinian (and less often Lamarckian) dynamics are regularly invoked to interpret cancer's multifarious molecular profiles, they shine little light on how tumorigenesis unfolds and often fail to fully capture the frequency and breadth of resistance mechanisms. This uncertainty frames one of the most problematic gaps between science and practice in modern times. Here, we offer a theory of adaptive cancer evolution, which builds on a molecular mechanism that lies outside neo-Darwinian and Lamarckian schemes. This mechanism coherently integrates non-genetic and genetic changes, ecological and evolutionary time scales, and shifts the spotlight away from positive selection towards purifying selection, genetic drift, and the creative-disruptive power of environmental change. The surprisingly simple use-it or lose-it rationale of the proposed theory can help predict molecular dynamics during tumorigenesis. It also provides simple rules of thumb that should help improve therapeutic approaches in cancer. specialized tumor evolution adaptation cell growth stress response natural selection environment cancer therapy 050 020 11 732081 [15 ] 2021 2234-943X https://www.documentation.ird.fr/hor/fdi:010082832 10.3389/fonc.2021.732081 2234-943X [F B010082832] https://www.documentation.ird.fr/hor/fdi:010082832 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2021-11/010082832.pdf IRD - Base Horizon / Pleins textes 2021-11-10 2025-02-24 fdi:010082832 fre