Review outlines genomic and epigenomic evolution in colorectal cancer

Colorectal cancer is a model for studying tumour evolution because it is accessible for sampling and progresses through recognizable morphological stages. This review synthesizes evidence on genomic, epigenomic and immune changes from initial transformation through metastasis and treatment resistance; it does not report a new clinical trial or patient cohort.

The authors describe a “Big Bang” pattern in which canonical driver mutations arise early, followed by largely neutral tumour expansion and genetic heterogeneity. Adenomas and carcinomas have similar driver-mutation burdens, while transition to carcinoma is associated with copy-number changes and epigenetic rearrangements. Metastases appear to arise from one or a few subclones, with phenotypic plasticity implicated in dissemination. Resistance can involve both genetic changes and reversible drug-tolerant cell states, and may be polyclonal.

The review also discusses immune selection and variation in tumour immunogenicity, including factors that may shape checkpoint-inhibitor response. Liquid-biopsy monitoring, molecular hyperselection and adaptive dosing are presented as emerging evolution-informed strategies, not established recommendations. As a review, the article summarizes existing evidence rather than testing these approaches prospectively; no new effect estimates or clinical outcomes are provided in the supplied text.