• Kazuhiro Shiba, Takayuki Matsumoto, and Seiichi Hirota.
• Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
• Gan To Kagaku Ryoho. 2009 Jul 1; 36 (7): 1080-5.

AbstractGastrointestinal stromal tumors (GISTs) are one of the representative diseases for which we now use small-molecule inhibitors against KIT and PDGFRs. Most GISTs have gain-of-function mutations of the c-kit or PDGFRA gene. The mutations result in constitutive receptor activation, and the activated receptor stimulates downstream signaling pathways. Because of resistance to conventional chemotherapy, the prognosis of patients with unresectable or metastatic GISTs has been very poor. The therapy of choice for resectable GIST is still surgery, but at present we can use imatinib, a selective tyrosine kinase inhibitor for KIT, PDGFRs and Bcr-Abl, for such advanced GIST patients. Although molecular target therapy has been very effective, secondary resistance to imatinib often develops during long-term imatinib administration. Secondary mutations of the c-kit gene in addition to primary c-kit gene mutation are a major cause of secondary resistance to imatinib. Now, we can use sunitinib for patients with imatinib-resistant GIST.

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