Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review

Abstract

Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors have significantly improved patient outcomes, their effectiveness is mostly limited to tumors with microsatellite instability (MSI-H/dMMR) or an increased tumor mutational burden, which comprise 10% of cases. Advancing personalized medicine in CRC hinges on identifying predictive biomarkers to guide treatment decisions. This comprehensive review examines established tissue markers such as KRAS and HER2, highlighting their roles in resistance to anti-EGFR agents and discussing advances in targeted therapies for these markers. Additionally, this review summarizes encouraging data on promising therapeutic targets and highlights the clinical utility of liquid biopsies. By synthesizing current evidence and identifying knowledge gaps, this review provides clinicians and researchers with a contemporary understanding of the biomarker landscape in CRC. Finally, the review examines future directions and challenges in translating promising biomarkers into clinical practice, with the goal of enhancing personalized medicine approaches for colorectal cancer patients.

Keywords: colorectal cancer; gene expression profiling; molecular targeted therapy; tumor biomarkers.

Figure 1

Current predictive biomarkers for metastatic colorectal cancer (CRC). EGFRi = EGFR inhibition; VEGFi = VEGF inhibition; G12Ci = KRAS G12C inhibition; BRAFi = BRAF inhibition; ICI = Immune checkpoint inhibition; HER2i = HER2 inhibition; CRC = colorectal cancer. (Created in Biorender.com).