BRAF mutations: signaling, epidemiology, and clinical experience in multiple malignancies

Cancer Control. 2014 Jul;21(3):221-30. doi: 10.1177/107327481402100307.


Background: Mutations in BRAF were first reported in 2002. Since that time, the molecular basis for oncogenic signaling has been elucidated in multiple malignancies. The development of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors has helped improve clinical outcomes in malignant melanoma and is suggested by case reports in other malignancies.

Methods: A review of pertinent articles examining the mechanisms of BRAF signaling in various cancer types and an update on clinical trials of BRAF inhibitions are presented.

Results: Clinical response to BRAF inhibition varies by malignancy. In melanoma, single-agent vemurafenib or dabrafenib prolongs overall survival compared with chemotherapy, but both are limited by the development of acquired resistance in many patients. Results of early-phase clinical trials and case reports demonstrate responses in V600E-mutant non-small-cell lung cancer, thyroid cancer, and hairy cell leukemia. However, no significant difference in progression-free survival was seen in colorectal cancer with single-agent vemurafenib. Overcoming resistance to BRAF inhibition with combination therapy is an active area of research.

Conclusions: The detection of BRAF mutations represents an advance in delivering molecularly targeted therapies to patients with a variety of cancers. Acquired resistance limits the ability of BRAF inhibitors to produce long-term remissions; however, combining BRAF inhibitors with the mitogen-activated protein kinase pathway and/or other pathway inhibitors represents a promising method to improve long-term outcomes.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mutation*
  • Neoplasms / enzymology*
  • Neoplasms / epidemiology
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Signal Transduction


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf