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Prophylactic surgery remains the primary intervention strategy, as there are currently no pharmacological treatment options for FAP patients. Previous therapeutic approaches have predominantly focused on reducing polyp size rather than preventing their initiation, thereby missing a key opportunity for early intervention. Crucially, to effectively target the earliest stages of tumour development requires a deeper understanding of the molecular mechanisms underlying adenoma formation. In this review, we evaluate the latest models and methods employed to investigate the origin of FAP adenomas. We describe how mutant cells expand from their initial emergence within the intestinal epithelium and how they compete with normal cells within intestinal crypts. In addition, we discuss how multiple mutant crypts cooperate to collectively form polyclonal adenomas, and how these polyclonal lesions gradually transition towards monoclonality as adenomas progress towards colorectal cancer. Finally, we highlight how these insights inform the development of targeted cancer prevention strategies for individuals with FAP.<\/jats:p>","DOI":"10.1007\/s10689-025-00479-3","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T21:00:13Z","timestamp":1748811613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redefining familial adenomatous polyposis: competition, cooperation, and the path to monoclonality"],"prefix":"10.1007","volume":"24","author":[{"given":"Sylvain","family":"Ferrandon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew F.","family":"Kalady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-5756","authenticated-orcid":false,"given":"Sanne M.","family":"van Neerven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"479_CR1","doi-asserted-by":"publisher","unstructured":"Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. 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