An updated review of colorectal cancer: Disease mechanisms, global burden, and novel treatment approaches

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, posing a significant public health challenge. The disease arises from a complex interplay of genetic, epigenetic, environmental, and lifestyle-related factors that drive the transformation of normal colonic epithelium into malignant tumours. The pathophysiology of CRC involves progressive molecular alterations, including chromosomal instability, microsatellite instability, and CpG island methylator phenotype, leading to dysregulation of critical signalling pathways such as Wnt/β-catenin, EGFR, PI3K/AKT, and TGF-β. Epidemiologically, CRC incidence varies across geographic regions, with higher prevalence in developed countries, although rapidly increasing trends are observed in developing nations due to changes in diet, physical inactivity, obesity, and aging populations.Treatment strategies for CRC depend on disease stage and include surgical resection, chemotherapy, radiotherapy, and targeted therapy. Conventional chemotherapeutic regimens such as fluoropyrimidines, oxaliplatin, and irinotecan remain the cornerstone of management; however, their clinical utility is often limited by toxicity and drug resistance. Recent advances have led to the development of innovative therapeutic approaches, including monoclonal antibodies targeting EGFR and VEGF pathways, immune checkpoint inhibitors, bispecific antibodies, antibody–drug conjugates, and mutation-selective small-molecule inhibitors. Emerging strategies such as circulating tumour DNA (ctDNA)-guided therapy, liquid biopsy, microbiome-targeted intervention, organoid-based drug testing, and artificial-intelligence-assisted diagnosis are reshaping the diagnostic and therapeutic landscape. This review provides a critical, updated overview of the pathophysiology, epidemiology, current treatment modalities, and recent innovations in CRC management, highlighting comparative evidence, limitations, and future directions for improved diagnosis and patient-centred care.