Dabrafenib and its potential for the treatment of metastatic melanoma

Drug Des Devel Ther. 2012;6:391-405. doi: 10.2147/DDDT.S38998. Epub 2012 Dec 11.


The purpose of this study is to review the development of BRAF inhibitors, with emphasis on the trials conducted with dabrafenib (GSK2118436) and the evolving role of dabrafenib in treatment for melanoma patients. Fifty percent of cutaneous melanomas have mutations in BRAF, resulting in elevated activity of the mitogen-activated protein kinase signaling pathway. Dabrafenib inhibits the mutant BRAF (BRAF(mut)) protein in melanomas with BRAF(V600E) and BRAF(V600K) genotypes. BRAF(V600E) metastatic melanoma patients who receive dabrafenib treatment exhibit high clinical response rates and compared with dacarbazine chemotherapy, progression-free survival. Efficacy has also been demonstrated in BRAF(V600K) patients and in those with brain metastases. Dabrafenib has a generally mild and manageable toxicity profile. Cutaneous squamous cell carcinomas and pyrexia are the most significant adverse effects. Dabrafenib appears similar to vemurafenib with regard to efficacy but it is associated with less toxicity. It is expected that new combinations of targeted drugs, such as the combination of dabrafenib and trametinib (GSK1120212, a MEK inhibitor), will provide higher response rates and more durable clinical benefit than dabrafenib monotherapy.

Keywords: BRAF inhibitor; BRAF mutation; GSK1120212; GSK2118436; clinical trial; vemurafenib.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Drug Design
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Indoles / adverse effects
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Neoplasm Metastasis
  • Oximes / adverse effects
  • Oximes / pharmacology
  • Oximes / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Vemurafenib


  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Oximes
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib