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, Michael Heinrich, Carol Beadling, J. Patterson, C. C. Bastida, S. C. Blackman, R. Kurzrock

    Research output: Contribution to journalArticle

    79 Citations (Scopus)

    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
    StatePublished - 2013

    Fingerprint

    Gastrointestinal Stromal Tumors
    Proto-Oncogene Proteins B-raf
    Exome
    Mutation
    Heterografts
    Adenosine Triphosphate
    Cell Line
    dabrafenib
    Therapeutics
    Neoplasms

    Keywords

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

    ASJC Scopus subject areas

    • Oncology

    Cite this

    BRAF mutant gastrointestinal stromal tumor : First report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance. / Falchook, G. S.; Trent, J. C.; Heinrich, Michael; Beadling, Carol; Patterson, J.; Bastida, C. C.; Blackman, S. C.; Kurzrock, R.

    In: Oncotarget, Vol. 4, No. 2, 2013, p. 310-315.

    Research output: Contribution to journalArticle

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    AU - Heinrich, Michael

    AU - Beadling, Carol

    AU - Patterson, J.

    AU - Bastida, C. C.

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