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Ref Type Journal Article
PMID (23470635)
Authors Falchook GS, Trent JC, Heinrich MC, Beadling C, Patterson J, Bastida CC, Blackman SC, Kurzrock R
Title BRAF mutant gastrointestinal stromal tumor: first report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance.
Journal Vol Issue Date Pages Journal Short Title
Oncotarget 4 2 2013 Feb 310-5 Oncotarget
URL
Abstract Text Activating oncogenic mutations of BRAF have been described in patients with gastrointestinal stromal tumor (GIST), but treatment of GIST with BRAF inhibitors and mechanisms of mediating the emergence of resistance in GIST have not been reported. Dabrafenib is a potent ATP-competitive inhibitor of BRAF kinase and is highly selective for mutant BRAF in kinase panel screening, cell lines, and xenografts. We report prolonged antitumor activity in the first patient with V600E BRAF-mutated GIST who was treated with a BRAF inhibitor. Whole exome sequencing performed in tumor tissue obtained at the time of progressive disease demonstrated a somatic gain-of-function PIK3CA mutation (H1047R) as well as a CDKN2A aberration, which may have contributed to eventual resistance to treatment.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E gastrointestinal stromal tumor predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in a 20% decrease in tumor size after 24 weeks in a patient with a gastrointestinal stromal tumor harboring BRAF V600E (PMID: 23470635). 23470635