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Defining and Targeting BRAF Mutations in Solid Tumors

  • Skin Cancer (T Ito, Section Editor)
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Opinion Statement

BRAF mutations are present in up to 8% of human cancers, and comprise a viable therapeutic target in many patients harboring these mutations. Specific BRAF-targeted therapies, such as vemurafenib, dabrafenib, and encorafenib, have transformed treatment of many BRAF-mutated cancers, producing meaningful clinical benefit with more tolerable safety profiles compared to prior standard-of-care treatments. BRAF inhibitors were first approved for use in metastatic melanoma, although resistance almost always limited their long-term effectiveness. Combination therapy with BRAF and MEK inhibitors has proven effective in delaying the onset of resistance, and produces additional clinical benefit across cancers. Although not promising initially in treatment of BRAF-mutated colorectal carcinoma, BRAF inhibitors in colorectal cancer were successfully combined with EGFR inhibitors, resulting in significant treatment response. Refining the use of BRAF and MEK inhibitors in less common tumor types (and for non-V600 mutations) and delaying the development of resistance remain pertinent future considerations in treating BRAF-mutated cancers. In this review, we will discuss the prevalence of BRAF mutations across human cancers and evidence on the efficacy and safety of current management strategies for various BRAF-mutant solid tumors.

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Funding

DBJ receives funding from NCI/NIH K23 CA204726.

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Authors and Affiliations

  1. Vanderbilt University School of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA

    Briana R. Halle BA

  2. Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN, 37232, USA

    Douglas B. Johnson MD

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  1. Briana R. Halle BA
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Correspondence to Douglas B. Johnson MD.

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Briana R. Halle declares that she has no conflict of interest. Douglas B. Johnson receives research funding from Bristol-Myers Squibb and Incyte Corporation, and serves on advisory boards for Array BioPharma, Bristol-Myers Squibb, Catalyst Pharmaceuticals, Iovance Biotherapeutics, Janssen Pharmaceutica, Merck, Novartis, and OncoSec.

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Halle, B.R., Johnson, D.B. Defining and Targeting BRAF Mutations in Solid Tumors. Curr. Treat. Options in Oncol. 22, 30 (2021). https://doi.org/10.1007/s11864-021-00827-2

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