Translational insights into gastrointestinal stromal tumor and current clinical advances

M. L. Hemming, Michael Heinrich, S. Bauer, S. George

    Research output: Contribution to journalArticle

    3 Scopus citations

    Abstract

    Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma of the gastrointestinal tract and, in the vast majority of cases, is characterized by activating mutations in KIT or, less commonly, PDGFRA. Mutations in these type III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the majority of KIT primary mutations respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib. However, drug resistance develops over time, most commonly due to secondary kinase mutations. Sunitinib and regorafenib are approved for the treatment of imatinib-resistant GIST in the second and third lines, respectively. However, resistance to these agents also develops and new therapeutic options are needed. In addition, a small number of GISTs harbor primary activating mutations that are resistant to currently available TKIs, highlighting an additional unmet medical need. Several novel and selective TKIs that overcome known mechanisms of resistance in GIST have been developed and show promise in early clinical trials. Additional emerging targeted therapies in GIST include modulation of cellular signaling pathways downstream of KIT, antibodies targeting KIT and PDGFRA and immune checkpoint inhibitors. These advancements highlight the rapid evolution in the understanding of this malignancy and provide perspective on the encouraging horizon of current and forthcoming therapeutic strategies for GIST.

    Original languageEnglish (US)
    Pages (from-to)2037-2045
    Number of pages9
    JournalAnnals of oncology : official journal of the European Society for Medical Oncology
    Volume29
    Issue number10
    DOIs
    StatePublished - Oct 1 2018

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    ASJC Scopus subject areas

    • Hematology
    • Oncology

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