Identifying and clinically validating biomarkers for immunotherapy in colorectal cancer

IntroductionColorectal cancer (CRC) is a leading cause of death. For three decades, chemotherapy with or without targeted therapy (provided before or after tumor resection surgery) has been the standard treatment for patients with CRC. Biomarkers are key tools for performing early detection, prognostication, and survival and treatment response predictions. Notably, immune checkpoint inhibitors (ICIs) have transformed prognoses for solid tumors (including CRC).Area coveredAlthough immunotherapy has developed considerably, it is only effective for a small number of microsatellite instability-high (MSIH) cancer cases; such cases represent only 5% of metastatic CRC (mCRC) cases, which are characterized by an immune-inflamed microenvironment that can be rewired against cancer cells through ICI administration. Immunotherapy research is gradually uncovering the mechanism underlying immune resistance in patients with CRC and discovering new biomarkers. For example, studies have clinically validated the associations of deficient mismatch repair system/microsatellite instability, tumor mutation burden, programmed death ligand 1 expression, and polymerase epsilon with CRC in patients undergoing immunotherapy.Expert opinionsClinical trials documenting the effect of immune checkpoints were performed to produce long-lasting effects for patients with mCRC. Consequently, therapeutic decision-making models are further refined by the inclusion of powerful molecular biomarkers in patients with CRC.

Automated summary

Colorectal cancer is a leading cause of death, and chemotherapy with or without targeted therapy is the standard treatment. Immune checkpoint inhibitors can be effective in a small portion of microsatellite instability-high colorectal cancer cases, but this represents only 5% of metastatic cases. Research on immunotherapy is uncovering mechanisms of immune resistance in colorectal cancer patients and discovering new biomarkers.