Improvements in Clinical Outcomes for <i>BRAF^V600E</i> -Mutant Metastatic Colorectal Cancer.

Abstract

Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. <i>BRAF^V600E</i> mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options. In colorectal cancer, <i>BRAF^V600E</i> mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type <i>BRAF</i> Success in treating other <i>BRAF^V600E</i> -mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer. Consequently, combination therapy with inhibitors of BRAF, MEK, and EGFR, which overcomes the innate treatment-resistant characteristics of <i>BRAF</i> ^V600E-mutant colorectal cancer, is now recommended by treatment guidelines.