title: Non-BRAF targeted therapies for melanoma: protein kinase inhibitors in Phase II clinical trials.
abstract: BACKGROUND
  Melanoma is one of the most aggressive forms of cutaneous malignancies displaying a substantial mortality rate among the various forms of skin cancers. The management of patients with advanced melanoma poses a significant challenge considering that the disease is refractory to most conventional therapies.
  
  
  METHODS
  This review highlights some of the genes and signaling molecules that are mutated in melanoma patients. The authors also discuss protein kinase inhibitors targeting non-BRAF mutations that are now being evaluated in Phase II clinical trials.
  
  
  CONCLUSIONS
  In light of several preclinical and clinical studies, it is clear that targeting single-gene mutations may not provide a desired therapeutic gain in the context of melanoma. Consequently, research will need to focus on rational combinations of novel therapeutic agents targeting multiple genetic aberrations or deregulated pathways to achieve a desired maximum clinical benefit. There is certainly a need for a better understanding of the complex and redundant molecular signatures associated with melanoma development; this would open up new avenues for creating the next generation of targeted and effective therapeutics.
authors: Virginia Commonwealth University, School of Medicine, Department of Human and Molecular Genetics , Richmond, VA , USA pbfisher@vcu.edu.
authors: Shilpa
authors: S
authors: Bhatia
authors: Luni
authors: L
authors: Emdad
authors: Swadesh K
authors: SK
authors: Das
authors: Hossein
authors: H
authors: Hamed
authors: Paul
authors: P
authors: Dent
authors: Devanand
authors: D
authors: Sarkar
authors: Paul B
authors: PB
authors: Fisher
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf