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Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution
journal contribution
posted on 2021-09-01, 00:00 authored by Francesco Catania, Beata UjvariBeata Ujvari, Benjamin Roche, Jean-Pascal Capp, Frederic ThomasAlthough 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
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Journal
Frontiers in OncologyVolume
11Article number
732081Pagination
1 - 15Publisher
FrontiersLocation
Lausanne, SwitzerlandPublisher DOI
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ISSN
2234-943XeISSN
2234-943XLanguage
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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ACQUIRED-RESISTANCEACUTE MYELOID-LEUKEMIAadaptationcancer therapycell growthCLONAL EVOLUTIONDRUG-RESISTANCEenvironmentGENE-EXPRESSIONLife Sciences & Biomedicinenatural selectionOncologyPASSENGER MUTATIONSREPLICATIVE LIFE-SPANScience & TechnologySOMATIC EVOLUTIONstress responseTRANSGENERATIONAL INHERITANCEtumor evolutionTUMOR MICROENVIRONMENT
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