| Mutation-driven drug development in melanoma. | |
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MedLine Citation:
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PMID: 20401974 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE OF REVIEW: The identification of mutations in signal transduction pathways that are central in melanoma pathophysiology has provided new therapeutic targets for drug development. The purpose of this review is to define those oncogenes for which there are preclinical data supporting clinical trials and to summarize results from clinical investigations. RECENT FINDINGS: CKIT mutations were first reported in 2005 but are present in only a small subpopulation of melanoma patients. The validation of inhibitors developed in gastrointestinal stromal tumors has taken several years, but recent evidence suggests that responses can be seen in CKIT mutant melanoma. First reported in 2002, BRAF is mutated in 50% of all melanomas and subsets of other cancers. The melanoma field is leading the clinical trials evaluating the value of targeting BRAF and MEK in BRAF mutant tumors. Results from the first clinical trial with a potent and selective BRAF inhibitor clearly show the therapeutic promise of this approach. SUMMARY: Larger clinical trials are needed to fully define the efficacy of BRAF and CKIT-directed therapy in melanoma, but early results suggest that this strategy will transform treatment options. Additional potential targets have been identified, and clinical trials evaluating novel drugs against them are underway. |
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Authors:
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Keith T Flaherty; F Stephen Hodi; Boris C Bastian |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current opinion in oncology Volume: 22 ISSN: 1531-703X ISO Abbreviation: Curr Opin Oncol Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-16 Completed Date: 2010-07-09 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 9007265 Medline TA: Curr Opin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 178-83 Citation Subset: IM |
Affiliation:
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Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. ktflaherty@partners.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Drug Design* Humans Melanoma / drug therapy*, genetics* Mutation* Signal Transduction / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA131524-02/CA/NCI NIH HHS; R01 CA131524-03/CA/NCI NIH HHS; R01 CA142873-02/CA/NCI NIH HHS |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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