BRAF mutant gastrointestinal stromal tumor: First report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance

G. S. Falchook, J. C. Trent, M. C. Heinrich, C. Beadling, J. Patterson, C. C. Bastida, S. C. Blackman, R. Kurzrock

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)310-315
Number of pages6
JournalOncotarget
Volume4
Issue number2
DOIs
StatePublished - 2013

Keywords

  • BRAF inhibition
  • BRAF mutation
  • Dabrafenib
  • Gastrointestinal stromal tumor
  • GSK2118436
  • V600E

ASJC Scopus subject areas

  • Oncology

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    Falchook, G. S., Trent, J. C., Heinrich, M. C., Beadling, C., Patterson, J., Bastida, C. C., Blackman, S. C., & Kurzrock, R. (2013). BRAF mutant gastrointestinal stromal tumor: First report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance. Oncotarget, 4(2), 310-315. https://doi.org/10.18632/oncotarget.864