Targeting the RAS pathway in melanoma

Trends Mol Med. 2012 Jan;18(1):27-35. doi: 10.1016/j.molmed.2011.08.001. Epub 2011 Sep 30.


Metastatic melanoma is a highly lethal type of skin cancer and is often refractory to all traditional chemotherapeutic agents. Key insights into the genetic makeup of melanoma tumors have led to the development of promising targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to be the central motor driving melanoma proliferation. Although recent clinical trials have brought enormous hope to patients with melanoma, adverse effects and novel escape mechanisms of these inhibitors have already emerged. Definition of the limits of the first successful targeted therapies will provide the basis for further advances in management of disseminated melanoma. In this review, the current state of targeted therapy for melanoma is discussed, including the potent BRAF(V600E) inhibitor vemurafenib.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
  • Signal Transduction / drug effects*


  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins p21(ras)