Pharmacological approaches for colitis associated colorectal cancer: a survey in preclinical studies

Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD), characterized by a unique inflammation-driven pathogenesis that distinguishes it from sporadic colorectal cancer. Despite advances in diagnostics and therapeutic interventions for IBD, effective preventive pharmacological treatments for CAC remain a critical unmet need. Drug discovery through the design and synthesis of novel molecules consumes considerable time and expense, especially for CAC in which no single enzyme, receptor, or gene dominates. Alternative approaches involve drug repurposing and application of natural compounds. The concurrent administration of multiple existing agents, as part of combination therapy, alongside the implementation of novel drug delivery systems such as nanocarriers, presents feasible and practical approaches for discovering effective treatments for CAC. After highlighting key molecular mechanisms in CAC pathogenesis, this review comprehensively surveys applied drug discovery approaches for CAC in preclinical studies. Our review highlights the importance of early and long-term intervention to prevent CAC, primarily by inhibiting the COX-2, STAT3, and NF-κB pathways associated with inflammation. Promising advances in CAC therapy involve the use of natural compounds and repurposed drugs, often administered in combination or through nanocarriers. These strategies aim to enhance therapeutic efficacy while minimizing toxicity.