Gastrointestinal stromal tumors (GISTs) are associated with a dismal prognosis in localized and advanced phase with a major resistance to conventional chemotherapy agents. GIST cells are positive for KIT (CD117) and CD34 in 100% and 70% of cases, respectively. Virtually all malignant GISTs actually harbor activating mutations of the kit pathway in the tumor cells, leading to ligand-independent activation of KIT tyrosine kinase activity and tumor growth in vitro. Glivec® inhibits KIT activity at an IC50 of approximately 100 nM which is similar to that required for inhibiting the tyrosine kinase associated with Bcr-abl and the PDGF receptor. Experiments on cell lines containing an activating juxtamembrane mutation (similar to that found in GISTs) and cell lines containing transfected wild type KIT protein, showed that these cells appear to be strongly dependent upon the activity of the mutant receptor to prevent apoptosis, thus providing further scientific justification for the development of Glivec® as an antineoplastic agent with specific activity against GIST as a KIT-driven malignancy.