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At least 70% of small cell lung cancers express the Kit receptor tyrosine kinase and its ligand, stem cell factor (SCF). Numerous lines of evidence have demonstrated that this coexpression constitutes a functional autocrine loop, suggesting that inhibitors of Kit tyrosine kinase activity could have therapeutic efficacy in this disease. STI571, formerly known as CGP 57148B, is a p.o. bioavailable 2-phenylaminopyrimide derivative that was designed as an Abl tyrosine kinase inhibitor, but also has efficacy against the platelet-derived growth factor receptor and Kit in vitro. Pretreatment of the H526 small cell lung cancer (SCLC)cell line with STI571 inhibited SCF-mediated Kit activation with an IC₅₀ of 0.1 μm as measured by inhibition of receptor tyrosine phosphorylation and 0.2 μm as measured by immune complex kinase assay. This paralleled the inhibition of SCF-mediated growth by STI571, which had an IC₅₀ of∼0 …