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

Abstract

Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract.¹ They occur predominantly in middle-aged and older persons, and approximately 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 elsewhere in the gastrointestinal tract.¹ Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product 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 tyrosine 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, uncontrolled cell proliferation, and stimulation of downstream 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