Paradoxical oncogenesis: are all BRAF inhibitors equal?

Pigment Cell Melanoma Res. 2013 Sep;26(5):611-5. doi: 10.1111/pcmr.12132. Epub 2013 Jul 19.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is a concerning toxicity with BRAF inhibitors in the treatment for melanoma. While the two drugs shown to improve survival, vemurafenib, and dabrafenib, have similar efficacy, the reported rates of cSCC are quite different. Drawing upon preclinical and clinical trial data, this article discusses the potential factors behind the different cSCC incidences reported with the two BRAF inhibitors and provides a strategic approach to understand this issue further.

Keywords: BRAF inhibitor; dabrafenib; melanoma; secondary malignancy; squamous cell carcinoma; vemurafenib.

MeSH terms

  • Carcinogenesis / drug effects*
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Oximes / pharmacology
  • Oximes / therapeutic use
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / pathology
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Vemurafenib

Substances

  • Imidazoles
  • Indoles
  • Oximes
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Vemurafenib
  • Proto-Oncogene Proteins B-raf
  • dabrafenib