Journal
BRITISH JOURNAL OF CANCER
Volume 90, Issue 9, Pages 1825-1829Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6601682
Keywords
IGF-1R; c-kit; co-targeting; small cell lung cancer; synergy
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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-1 receptor (IGF-1R) signalling, tyrphostins AG 1024 and 1296 ( inhibitors of IGF-1R 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-1R and c-kit in SCLC may be more effective than single-agent therapies.
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