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Gastrointestinal Stromal Tumor

Abstract

Gastrointestinal stromal tumor (GIST) is considered to be driven by a gain-of-function mutation mainly in the KIT or PDGFRA gene. And these mutations were reported to cause ligand-independent constitutive activation of receptor tyrosine kinase, KIT and PDGFR-α, and subsequently activate common downstream signaling pathways, including ERK kinases, PI3kinase-mTOR pathways, and STATs pathways. These mutations have been reported to be related with various clinicopathological features of tumors. In addition, these findings have facilitated the development of targeted therapies with tyrosine kinase inhibitors and the revolutionary chemotherapeutic drug imatinib mesylate. Its efficacy also greatly depends on the genotype of GIST. The drug, however, met intrinsic or acquired resistance during the treatment, of which the molecular mechanisms were mostly dependent on the genotype of GIST, including primary mutations or secondary mutations in the kinase domains of the corresponding target genes, respectively. Furthermore, the efficacies of second-line and third-line therapy might correlate with the type of secondary mutations in some reports. This article focuses on the recent findings of genetics in GIST.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Tsuyoshi Takahashi

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Correspondence to Tsuyoshi Takahashi .

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  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Yukinori Kurokawa

  2. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Hokkaido, Japan

    Yoshito Komatsu

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Takahashi, T. (2019). Genetics. In: Kurokawa, Y., Komatsu, Y. (eds) Gastrointestinal Stromal Tumor. Springer, Singapore. https://doi.org/10.1007/978-981-13-3206-7_3

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  • DOI: https://doi.org/10.1007/978-981-13-3206-7_3

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