Molecular Approaches for Targeting BRAF in Metastatic Colorectal Cancer

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Oncogenic mutations in B-type Raf kinase (BRAF) occur in 7% to 10% of metastatic colorectal cancers (mCRC). Despite recent improvements in survival for the general population of patients with mCRC, patients with BRAF-mutant mCRC continue to have poor response to most systemic therapies, and prognosis remains poor. There is a substantial unmet need for novel therapeutic strategies to treat patients with BRAF-mutant mCRC.

In a recent review, the epidemiology, molecular pathogenesis, prognosis, and mechanisms of treatment resistance of BRAF mutated CRC is outlined. This review highlights that aggressive chemotherapy combinations (FOLFOXIRI plus bevacizumab), combinations of chemotherapy and targeted therapy (irinotecan plus cetuximab and vemurafenib), and triplet targeted therapy combinations (BRAF + EGFR + MEK inhibitors) may be particularly beneficial. Additionally, an evidence-based treatment algorithm for BRAF-mutated mCRC is proposed. Finally, this review highlights novel therapeutic strategies aimed at enhancing response and improving the survival and quality of life in patients with BRAF-mutated mCRC.

http://www.sciencedirect.com/science/article/pii/S0305737217301299