Colorectal Cancer Biomarkers: The Expanding Landscape

Colorectal cancer (CRC) remains one of the most common malignancies worldwide and a leading cause of cancer-related mortality. Recent advances in CRC molecular biology have focused on biomarkers for early detection, prognostic stratification, treatment selection, and disease monitoring. Clinically validated biomarkers, including microsatellite instability (MSI), RAS and BRAF mutations, HER2 amplification, and carcinoembryonic antigen (CEA), guide targeted therapy and predict treatment response. However, tumor heterogeneity, clonal evolution, and microenvironmental influences limit the predictive value of single biomarkers. Recent molecular diagnostics therefore increasingly focus on dynamic and minimally invasive approaches. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease, monitoring recurrence, and assessing tumor evolution in real time. Multi-omics profiling, spatial transcriptomics, and artificial intelligence further expand tumor characterization except for conventional genomic alterations. Our review integrates common CRC biomarkers with developing liquid biopsy, multi-omics, spatial transcriptomics, and artificial intelligence approaches across early detection, prognosis, treatment selection, and longitudinal monitoring. Future biomarker strategies will likely rely on integrated molecular models combined with longitudinal liquid-biopsy assessment. However, most new biomarkers remain at the investigational stage, and assay heterogeneity, limited standardization, and insufficient prospective clinical validation currently restrict their routine clinical use.