Improvements in clinical outcomes for BRAF^V600E-mutant metastatic colorectal cancer

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. BRAF^V600E 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, BRAF^V600E mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF. Success in treating other BRAF^V600E-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 BRAF^V600E-mutant colorectal cancer, is now recommended by treatment guidelines.