The Genetic Landscape of Colorectal Cancer: From Molecular Alterations to Therapeutic Decision Pathways

Abstract

Simple Summary Colorectal cancer is no longer considered a single disease but rather a collection of biologically distinct tumor subtypes characterized by specific genetic alterations. These molecular differences have transformed patient management by enabling personalized treatment strategies based on individual tumor profiles. This review summarizes the most clinically relevant genetic biomarkers currently used in colorectal cancer, including microsatellite instability, RAS and BRAF mutations, HER2 amplification, and NTRK fusions, while also discussing emerging biomarkers such as circulating tumor DNA, tumor mutational burden, transcriptomic signatures, microbiome-derived markers, epigenetic alterations, and artificial intelligence-based prediction models. We propose a practical framework that categorizes biomarkers according to their current clinical applicability and future translational potential. Understanding how these biomarkers influence diagnosis, prognosis, treatment selection, and disease monitoring may help clinicians and researchers navigate the rapidly evolving landscape of precision oncology and support the development of more individualized approaches for patients with colorectal cancer.