Precision Medicine for the Treatment of Colorectal Cancer: the Evolution and Status of Molecular Profiling and Biomarkers

Purpose of Review The application of advanced genomic testing to develop tumor-specific molecular profiles is essential to facilitating precision medicine pharmacotherapy. These approaches are highly relevant in colorectal cancer, where tumors frequently contain druggable molecular mutations, as well as the potential to respond to immunotherapy. Here we review the literature characterizing biomarker-driven pharmacotherapy for colorectal cancer, and highlight the pivotal ongoing trials that will help inform future treatment of this disease. Recent Findings Both prospective and retrospective studies have confirmed that the benefit from adding anti-epidermal growth factor receptor therapy is limited to patients with stage IV disease, RAS wild-type tumors, and left-sided primary tumors. Furthermore, patients with BRAF-mutated tumors derive significantly less benefit from the addition anti-epidermal growth factor receptor therapy. The use of BRAF inhibitors in the second-line setting is associated with a relatively high response rate, and regimens incorporating first-line treatment with BRAF inhibitors may soon become standard of care for patients with BRAF-mutated tumors. In the relapsed setting, the use of targeted agents and immunotherapy should be prioritized for patients with respective tumor profiles. There has been significant advancement in the understanding of how to utilize molecular profiling and tumor biomarkers to tailor pharmacotherapy in colorectal cancer. Future studies should continue to incorporate these tests at enrollment to further define patient cohorts deriving the greatest benefit from precision medicine, characterize ideal sequence of therapy, and advance understanding of drug resistance mechanisms.