title: The MAPK pathway in melanoma.
abstract: OBJECTIVE
  As understanding of molecular and genetic processes in cancer evolves, so does appreciation of tumor heterogeneity. Tumor profiling has expanded knowledge of relevant pathways, and their interplay. Similar to the revolution in breast cancer with the discovery and successful therapeutic targeting of HER2/neu, the melanoma field is rapidly evolving. The MAPK pathway is dysregulated in most melanomas. Several therapeutic agents directed against this pathway are in development. This review summarizes current understanding of the MAPK pathway in melanoma biology and therapeutic strategies.
  
  
  RESULTS
  Recent data support the concept of distinct groups of molecular and genetic abnormalities in melanomas, related to type of sun exposure and body site. MAPK abnormalities, specifically BRAF or NRAS mutations, are most prevalent. The efficacy of sorafenib, a multitargeted kinase inhibitor, in melanoma is still under evaluation. While ineffective as a single agent, efficacy in combination with chemotherapy or targeted agents is being assessed. More specific inhibitors of BRAF, or other MAPK members, may prove more effective.
  
  
  CONCLUSIONS
  Tumor profiling has led to exciting advances. The MAPK pathway is one of several potentially targetable pathways in melanoma. Ultimately, combinatorial therapeutics against relevant disrupted pathways in specific tumors likely will prove most successful.
authors.affiliation: University of Pennsylvania, Division of Hematology and Oncology, Department of Medicine, The Abramson Cancer Center, Philadelphia, Pennsylvania 19104, USA. leslie.fecher@uphs.upenn.edu
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Fecher
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Amaravadi
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
mesh_terms: D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020928:Mitogen-Activated Protein Kinases