Co-targeting IGF-IR and c-kit: Synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Abstract

Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC growth is also driven by insulin-like growth factor-I receptor (IGF-I R) signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-IR and c-kit activity, respectively) were used to co-target these receptors in H 209 SCLC cells. Combination treatment caused synergy in proliferation inhibition and in apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2, suggesting that co-targeting IGF-IR and c-kit in SCLC may be more effective than single-agent therapies. © 2004 Cancer Research UK.