Precision medicine for metastatic colorectal cancer: an evolving era

ABSTRACT

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:

• Colorectal Cancer
• anti-EGFR
• mismatch repair genes
• MSI-H
• MMR-D
• BRAF
• HER2
• BRCA
• PALB2
• POLE
• POLD1
• NTRK
• ALK
• ROS1
• FGFR
• immunotherapy
• immune checkpoint inhibitors
• precision medicine

Article highlights

• Metastatic colorectal cancer is a highly challenging disease with limited targeted therapeutic options.

• Immune checkpoint inhibitors have led to promising clinical outcomes in colorectal cancer patients with MSI-H/MMR-D disease. Future approaches with combined modalities may lead to further improvement in this subset of colorectal cancer patients.

• Recent advances in genome sequencing technology have advanced our understanding of the molecular heterogeneity of colorectal cancer and thus has created therapeutic opportunities for alterations in actionable genes such as BRAF, HER2, NTRK, POLE, and POLD1.

• The future will likely bring more therapeutic opportunities, that are based on molecular alterations, to precision medicine.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.