Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib

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Abstract
Imatinib mesylate is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). We monitored the serum levels of KIT, KIT ligand (stem cell factor, SCF), and the vascular endothelial growth factor (VEGF) in patients with advanced GISTs treated with imatinib in a prospective randomized trial. Patients with GISTs (n = 66) had elevated pretreatment serum KIT and VEGF levels as compared with controls (median, 292 AU/mL [409 ng/mL] vs 238 AU/mL [333 ng/mL], P = .037; and median, 303 pg/mL vs 190 pg/mL, P = .013, respectively), but lower levels of SCF (median, 645 pg/mL vs 950 pg/mL; P ≤ .0001). After 1 and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from pretreatment levels, whereas SCF levels increased 11% and 33%, respectively. Serum VEGF levels decreased during treatment in responding patients. The median serum SCF/KIT ratio increased with treatment duration, and was 7.7-fold higher after 12 months of treatment than at baseline (range, 3.1-259-fold). A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. (Blood. 2004;103:2929-2935)