Precision medicine for metastatic colorectal cancer in clinical practice

Abstract

Globally, metastatic colorectal cancer is one of the leading causes for cancer-related death. Treatment limited to conventional chemotherapeutics extended life for only a few months. However, advances in surgical approaches and medical treatment regimens have greatly increased survival, even leading to long-term remission in selected patients. Advances in multiomics analysis of tumors have built a foundation for molecular-targeted therapies. Furthermore, immunotherapies are on the edge of revolutionizing oncological practice. This review summarizes recent advances in the growing toolbox of personalized treatment for patients with metastatic colorectal cancer. We provide an overview of current multimodal therapy and explain novel immunotherapy and targeted therapy approaches in detail. We emphasize clinically relevant therapies, such as inhibitors of MAPK signaling, and give recommendations for clinical practice. Finally, we describe the potential predictive impact of molecular subtypes and provide an outlook on novel concepts, such as functional precision medicine.

Keywords: chemotherapy; colorectal cancer; consensus molecular subtypes; immunotherapy; organoids; patient-derived xenografts; personalized oncology; precision medicine; targeted therapy.

Figure 1.

Combination strategies to enhance immune checkpoint inhibitor efficacy in pMMR colorectal cancers tested in current clinical trials.

Figure 2.

Targeting the MAPK pathway in colorectal cancer. Druggable receptors and intracellular signaling components of the pathway are depicted. Drugs targeting the pathway discussed in the text are highlighted. T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan.