MEK inhibitors and their potential in the treatment of advanced melanoma: The advantages of combination therapy

Khiem A. Tran, Michelle Y. Cheng, Anupam Mitra, Hiromi Ogawa, Vivian Y. Shi, Laura P. Olney, April M. Kloxin, Emanual Michael Maverakis

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalDrug Design, Development and Therapy
Volume10
DOIs
StatePublished - Dec 21 2015

Keywords

  • BRAF inhibitor
  • Cobimetinib
  • Dabrafenib
  • MAPK
  • Pathway
  • Trametinib
  • Vemurafenib

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

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