Colitis-associated colorectal carcinogenesis: molecular mechanisms and therapeutic potential

Chronic colitis is a major risk factor for colorectal cancer (CRC), particularly for colitis-associated colorectal cancer (CAC), where persistent inflammation drives the transition from mucosal injury to malignant transformation. Accumulating evidence indicates that gut microbiota dysbiosis, epithelial barrier disruption, microbial translocation, chronic immune activation, and aberrant inflammatory signaling collectively contribute to CAC initiation and progression. Sustained inflammation promotes oxidative stress, DNA damage, genetic/epigenetic alterations, and tumor microenvironment remodeling, ultimately facilitating tumor development and immune evasion. These processes form an interconnected pathogenic network linking microbial, inflammatory, genetic, immune, and stromal alterations. This review comprehensively summarizes the key drivers and molecular mechanisms of CAC, covering microbiota and barrier dysfunction, inflammatory signaling, oxidative stress and DNA damage, genetic and epigenetic alterations, and tumor microenvironment remodeling and immune dysregulation. We further review recent advances in diagnostic biomarkers, disease monitoring, chemoprevention, targeted therapies, and emerging interventions, including the potential utility of specific chemokine axes as biomarkers and therapeutic targets. Particular emphasis is placed on the translational challenges of linking mechanistic insights to diagnostic and therapeutic advances, including biomarker validation, stage-specific interventions, and patient stratification across disease progression. By integrating these interconnected mechanisms and therapeutic strategies, this review provides a comprehensive framework for understanding CAC pathogenesis and identifies opportunities for precision prevention, early detection, and multimodal treatment.