Introduction: Metastatic colorectal cancer (CRC) remains a dilemma for cancer researchers with an increasing incidence in the younger patient population. Until the last decade, limited therapeutic options were available for metastatic CRC patients leading to relatively poor clinical outcomes.Areas covered: With advances in genome sequencing technology and reductions in the cost of next-generation sequencing, molecular profiling has become more accessible for cancer researchers and clinical investigators, which has furthered our understanding of the molecular behavior of CRC. This progress has recently translated into significant advances in molecular-based therapeutics and led to the development of new target-specific agents in metastatic CRC patients. In this review article, we extensively elaborate on genomic alterations seen in CRC patients including, but not limited to, EGFR, MMR, BRAF, HER2, NTRKs, FGFR, BRCA1/2, PALB2, POLE, and POLD1 genes, all of which are potentially actionable by either an FDA-approved agent or in a clinical trial setting.Expert opinion: We strongly recommend molecular profiling in metastatic CRC patients during the early course of their disease, as this may provide therapeutic and prognostic information that can guide clinicians to practice precision medicine. Patients with potentially actionable genes should be considered for targeting agents based on molecular alterations.
Keywords: ALK; BRAF; BRCA; Colorectal Cancer; FGFR; HER2; MMR-D; MSI-H; NTRK; PALB2; POLD1; POLE; ROS1; anti-EGFR; immune checkpoint inhibitors; immunotherapy; mismatch repair genes; precision medicine.