Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor

Abstract

G ASTROINTESTINAL stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract. 1 They occur predomi- nantly in middle-aged and older persons, and ap- proximately 70 percent of the tumors are found in the stomach, 20 to 30 percent are found in the small intestine, and less than 10 percent are found else- where in the gastrointestinal tract. 1 Recent studies have shown that cells in gastrointestinal stromal tu- mors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the prod- uct of the proto-oncogene c- kit, can be detected by immunohistochemical staining for CD117, which appears to be the most specific diagnostic criterion for the diagnosis of gastrointestinal stromal tumors. 2 The ligand for the c-kit receptor is stem-cell factor, also known as steel factor or c-kit ligand. 3 Mutations of c- kit that cause constitutive activation of the ty- rosine kinase function of c-kit are detectable in most gastrointestinal stromal tumors and appear to play a central part in the pathogenesis of these tumors. 4,5 These mutations result in ligand-independent tyrosine kinase activity, autophosphorylation of c-kit, uncon- trolled cell proliferation, and stimulation of down- stream signaling pathways, including those involving phosphatidylinositol 3-kinase and mitogen-activated protein kinases. Gastrointestinal stromal tumors are notoriously unresponsive to cancer chemotherapy, and there is no effective therapy for advanced, metastatic disease. 6 We used STI571 (Glivec, Novartis, Basel, Switzer- land), 7 an inhibitor of the tyrosine kinase activity of c-kit, in a patient with a gastrointestinal stromal tumor.