Precision oncology in colorectal cancer: Integrating molecular subtyping, multidisciplinary management, and emerging therapeutics

Colorectal cancer (CRC) remains a leading cause of cancer incidence and mortality globally, presenting substantial clinical challenges attributable to its intricate pathogenic mechanisms and the broad spectrum of available treatment modalities. Recent breakthroughs in molecular biology have markedly advanced our understanding of the genetic and epigenetic alterations driving CRC initiation and progression. These discoveries have unraveled critical oncogenic drivers that promote tumorigenesis and precisely identified promising therapeutic targets, laying a solid foundation for the advancement of precision medicine in CRC management. This review highlights the latest progress in deciphering the molecular underpinnings of CRC, with a specific focus on the roles of gene mutations and epigenetic regulation in tumor initiation, progression, and metastasis. Additionally, it provides a comprehensive evaluation of current multidisciplinary treatment strategies, including surgical resection, chemoradiotherapy, targeted therapies, and immunotherapies, while systematically discussing their clinical efficacy, safety profiles, and inherent limitations. Notably, the review emphasizes the pivotal correlation between tumor molecular characteristics and treatment responses, underscoring the clinical imperative of personalized therapeutic approaches for CRC patients. Despite significant strides in improving patient outcomes over the past decade, considerable challenges persist, such as the development of acquired drug resistance, intratumoral and intertumoral heterogeneity, and variable treatment responsiveness across distinct molecular subtypes. By integrating cutting-edge molecular insights with clinical therapeutic strategies, this review aims to establish a robust theoretical framework for CRC management and delineate future research directions that may further enhance therapeutic efficacy and improve long-term patient prognosis. • Recent breakthroughs have elucidated critical genetic and epigenetic alterations that drive colorectal cancer pathogenesis. • A comprehensive, multidisciplinary approach to treatment now integrates surgical resection, chemoradiotherapy, targeted therapy, and immunotherapy. • The connection between molecular characteristics and treatment responses underscores the central role of personalized, precision medicine. • Significant clinical challenges persist, including drug resistance, tumor heterogeneity, and variable efficacy across different molecular subtypes.