Comprehensive Overview of Therapeutic Strategies in Colon Cancer: Chemotherapy, Targeted Therapy, and Immunotherapy

Colon cancer remains a leading global health challenge driven by substantial molecular heterogeneity, complex carcinogenic pathways, and the persistent emergence of therapeutic resistance. This review provides a comprehensive and integrative synthesis of contemporary treatment strategies spanning conventional chemotherapy, molecularly targeted agents, and immunotherapy while contextualizing them within the biological mechanisms that shape therapeutic response. We dissect the mechanistic underpinnings and clinical performance of foundational regimens such as FOLFOX, FOLFIRI, and CAPOX, and analyze how key driver alterations, including RAS/RAF mutations, HER2 amplification, MSI/MMR status, and VEGF-mediated angiogenesis, influence disease progression and therapeutic selection. In addition, we analyze shared resistance pathways and the mechanistic rationale supporting rational combination strategies, including BRAF/EGFR/MEK blockade, HER2-directed dual targeting, and PD-1/PD-L1-based combinations aimed at overcoming immune exclusion in MSS tumors. Emerging advances such as KRAS G12C inhibitors, multi-kinase angiogenesis modulators, antibody-drug conjugates, ribosome biogenesis inhibitors, AI-guided therapeutic algorithms, and ctDNA-based monitoring are also discussed. By integrating mechanistic insights with clinical evidence, this review offers a structured framework to better understand current treatment paradigms and future directions in biomarker-driven precision therapy for colon cancer.