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This review synthesizes current advances in CRC epidemiology, risk factors, signaling biology, clinical presentation, screening, diagnosis, and management across the care continuum. We frame CRC as a systems\u2010level disease in which genomic instability, epigenetic dysregulation, metabolic remodeling, tumor microenvironmental evolution, and gut microbiota interactions converge on interconnected pathways, including Wnt\/\u03b2\u2010catenin, MAPK, PI3K\/AKT\/mTOR, TGF\u2010\u03b2, and immune\u2010regulatory networks. We distinguish established standards of care from recent practice\u2010changing developments and investigational strategies. Within this framework, we discuss blood\u2010based screening, AI\u2010assisted endoscopy, ctDNA\u2010informed residual disease assessment, biomarker\u2010defined molecular workup, immunotherapy strategies for dMMR disease, and targeted approaches for KRAS G12C\u2010mutated, BRAF V600E\u2010mutated, and HER2\u2010positive metastatic CRC. Despite substantial progress, major challenges remain, including limited immunotherapy benefit in microsatellite\u2010stable CRC, unequal access to high\u2010quality screening and molecular testing, and uncertainty regarding implementation of newer biomarkers across diverse populations. An integrated framework linking population risk, tumor ecology, evidence\u2010based biomarker use, and equitable precision care is essential for the next phase of CRC prevention and management.<\/jats:p>","DOI":"10.1002\/mco2.71028","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:09:31Z","timestamp":1790924971000},"source":"Crossref","is-referenced-by-count":0,"title":["Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-5334","authenticated-orcid":false,"given":"Kairui","family":"Wan","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, School of Medicine Chongqing University  Chongqing 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