title: Selecting patients for KIT inhibition in melanoma.
abstract: For many years, melanoma has been regarded as a single disease in terms of therapeutic considerations. The more recent identification of multiple molecular mechanisms underlying the development, progression, and prognosis of melanoma has led to a new paradigm for the management of this disease, has created new therapeutic opportunities, and has led to improved clinical outcomes. Such advances, however, are dependent upon methods that can reproducibly identify key molecular alterations within an individual tumor, define clinically relevant genetic subgroups of disease, and permit improved patient selection for targeted therapies.Melanomas harboring genetic alterations of KIT have been demonstrated to constitute one such molecular subgroup of disease. In this chapter, we will discuss the biology of KIT in melanoma, review the rationale for and clinical data regarding KIT inhibition in melanomas harboring activating alterations of KIT, propose guidelines for the selection of patients for KIT inhibitor therapy, and, finally, present laboratory methods for KIT assessment in melanoma.
authors.affiliation: Melanoma/Sarcoma Medical Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000378:metabolism; D004273:DNA, Neoplasm / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology*; D016612:Paraffin Embedding; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D012996:Solutions
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D012996:Solutions; D019009:Proto-Oncogene Proteins c-kit