Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines.

Human malignant mesothelioma (HMM) is a fatal tumor and is poorly responsive to current therapeutic regimens. The insulin-like growth factor 1 receptor (IGF-1R) pathway is activated in HMM cell lines and tissues. Treatment with AG1024, an inhibitor of the IGF-1R pathway, significantly decreased cell proliferation and attenuated the phosphorylation of Akt and p44/42. In addition, it significantly enhanced the cytotoxic effects of cisplatin in HMM cell lines. This study supports the conjecture that inhibition of the IGF-1R pathway may be a useful target for reducing toxicity and alleviating chemoresistance to traditional anticancer drugs in HMM patients.