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Annu Rev Pathol. 2008;3:557-86.

Molecular pathobiology of gastrointestinal stromal sarcomas.

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  • 1Department of Pathology, Oregon Health & Science University Cancer Institute, Portland, OR 97239, USA corlessc@ohsu.edu


Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas whose unique pathobiology provides a model of how molecularly targeted therapeutics can have a major impact on patient welfare. Approximately 85% of GISTs are driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT or platelet-derived growth factor receptor alpha. We review the pivotal relationship between specific mutations in these kinase genes, the origin and pathologic spectrum of GISTs, and the response of these tumors to treatment with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance to kinase inhibitor therapy are discussed, and targets for the next generation of therapeutics are considered. The rapid evolution in our understanding of GISTs, which stems directly from the close alliance of basic and clinical researchers in the field, illustrates the growing role of the molecular classification of solid tumors in the development of modern oncological treatments.

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