title: Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics.
abstract: Despite multiple clinical trials utilizing a spectrum of therapeutic modalities, melanoma remains a disease with dismal outcomes in patients with advanced disease. However, it is now clear that melanoma is not a single entity, but can be molecularly divided into subtypes that generally correspond to the anatomical location of the primary melanoma. Melanomas from acral lentiginous, mucosal, and chronic sun-damaged sites frequently harbor activating mutations and/or increased copy number in the KIT tyrosine kinase receptor gene, which are very rare in the more common cutaneous tumors. Multiple case reports and early observations from clinical trials suggest that targeting mutant KIT with tyrosine kinase inhibitors is efficacious in KIT mutant melanoma. This review recounts what is known about the role of KIT in melanocyte maturation, our current understanding of KIT genetic aberrations in melanoma, and how this knowledge is being translated into clinical oncology.
authors.affiliation: Departments of Melanoma Medical Oncology and Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. swoodman@mdanderson.org
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D019009:Proto-Oncogene Proteins c-kit
references.citation: EMBO J. 1987 Nov;6(11):3341-51
references.pmid: 2448137
references.citation: Br J Haematol. 2007 Jul;138(1):12-30
references.pmid: 17555444
references.citation: Br J Cancer. 2008 Dec 16;99(12):2065-9
references.pmid: 19018266
references.citation: J Invest Dermatol. 2006 May;126(5):1102-10
references.pmid: 16410786
references.citation: Hum Pathol. 2005 May;36(5):486-93
references.pmid: 15948115
references.citation: Hum Pathol. 2006 May;37(5):520-7
references.pmid: 16647948
references.citation: J Physiol. 2007 Jan 1;578(Pt 1):33-42
references.pmid: 17095561
references.citation: J Clin Oncol. 2004 Nov 15;22(22):4514-22
references.pmid: 15542802
references.citation: Mol Cancer Ther. 2009 Aug;8(8):2079-85
references.pmid: 19671763
references.citation: Cell. 1988 Oct 7;55(1):185-92
references.pmid: 2458842
references.citation: Pigment Cell Melanoma Res. 2008 Aug;21(4):492-3
references.pmid: 18510589
references.citation: Clin Cancer Res. 2008 Nov 1;14(21):6821-8
references.pmid: 18980976
references.citation: N Engl J Med. 2004 Sep 2;351(10):998-1012
references.pmid: 15342808
references.citation: Nature. 1986 Apr 3-9;320(6061):415-21
references.pmid: 3007997
references.citation: Blood. 1995 Feb 1;85(3):641-9
references.pmid: 7530502
references.citation: Clin Cancer Res. 2008 Dec 1;14(23):7726-32
references.pmid: 19047099
references.citation: Stem Cells. 2005;23(1):16-43
references.pmid: 15625120
references.citation: Nature. 1988 Sep 1;335(6185):88-9
references.pmid: 2457811
references.citation: Mol Biol Cell. 1992 Mar;3(3):349-62
references.pmid: 1378327
references.citation: Virchows Arch. 2008 Jan;452(1):27-32
references.pmid: 18066592
references.citation: Oncogene. 1992 Jan;7(1):51-6
references.pmid: 1371338
references.citation: Nat Clin Pract Oncol. 2008 Dec;5(12):737-40
references.pmid: 18936790
references.citation: Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48
references.pmid: 15526160
references.citation: J Clin Oncol. 2006 Sep 10;24(26):4340-6
references.pmid: 16908931
references.citation: Trends Genet. 1993 Aug;9(8):285-90
references.pmid: 7691001
references.citation: EMBO J. 1991 Sep;10(9):2451-9
references.pmid: 1714377
references.citation: Am J Hum Genet. 1992 Feb;50(2):261-9
references.pmid: 1370874
references.citation: Cancer. 2006 May 1;106(9):2005-11
references.pmid: 16565971
references.citation: Mod Pathol. 2009 Nov;22(11):1446-56
references.pmid: 19718013
references.citation: Int J Cancer. 2007 Jul 15;121(2):257-64
references.pmid: 17372901
references.citation: Br J Cancer. 2008 Sep 2;99(5):734-40
references.pmid: 18728664
references.citation: Int J Cancer. 2009 Feb 15;124(4):862-8
references.pmid: 19035443
references.citation: N Engl J Med. 2005 Nov 17;353(20):2135-47
references.pmid: 16291983
references.citation: Br J Cancer. 2005 Apr 25;92(8):1398-405
references.pmid: 15846297
references.citation: J Endocrinol Invest. 2000 Oct;23(9):609-15
references.pmid: 11079457
references.citation: J Clin Oncol. 2008 Apr 20;26(12):2046-51
references.pmid: 18421059
references.citation: Blood. 1993 Aug 15;82(4):1151-8
references.pmid: 7688988
references.citation: Oncogene. 1996 Dec 5;13(11):2339-47
references.pmid: 8957075
references.citation: Oncogene. 2010 Jan 14;29(2):227-36
references.pmid: 19802003
references.citation: Annu Rev Pathol. 2008;3:557-86
references.pmid: 18039140
references.citation: Pigment Cell Melanoma Res. 2010 Feb;23(1):14-26
references.pmid: 20025711
references.citation: Mol Cancer Res. 2009 Sep;7(9):1525-33
references.pmid: 19737976