Clinical Utility of BRAF-Targeted Therapy in Melanoma

Jeffrey A. Sosman*, Douglas B. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The identification of BRAFV600mutations in melanoma rapidly translated into a search for strategies to exploit this recurrent genetic alteration. The selective BRAF inhibitors, vemurafenib and dabrafenib have demonstrated impressive antitumor activity with objective response rates of approximately 50 % and improved progression-free and/or overall survival compared to cytotoxic chemotherapy. The MEK inhibitor trametinib also subsequently demonstrated improved survival compared to chemotherapy. Acquired resistance, however, has limited the long-term antitumor efficacy of these therapies. Combined BRAF and MEK inhibition represents one strategy to delay the onset of resistance and potentially extend survival. Additional BRAF and MEK inhibitors and combinations are being developed with a goal of improving outcomes further. In this chapter, we review the development of approved BRAF and MEK inhibitors, the experience with combination therapy, and special clinical situations for BRAF-targeted therapy.

Original languageEnglish (US)
Pages (from-to)67-84
Number of pages18
JournalCancer Drug Discovery and Development
Volume82-168
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • BRAF inhibitor
  • BRAF-mutant
  • Dabrafenib
  • MEK inhibitor
  • Melanoma
  • Trametinib
  • Vemurafenib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Clinical Utility of BRAF-Targeted Therapy in Melanoma'. Together they form a unique fingerprint.

Cite this