GSK 1838705A

Meningioma cell growth is critically dependent on autocrine miR-483/IGF-2 stimulation and the IGF-2 pathway provides a feasible meningioma treatment target.

Our data clearly demonstrated that adipocytes, the major compartment of tumor stroma, further sustain the aggressive malignant phenotype of mutant cells, mainly involving IGF-1R signaling pathway. Prospectively our findings address the use of an IGF-1R inhibitor to block the mutant/stroma cells interplay. In the era of precision medicine, the use of a specific IGF1R inhibitor may help to improve the outcome of BC patients expressing the ESR1 mutations, particularly in obese setting.

Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.