Taken together, our results suggest that IGF1R and the downstream PI3K/AKT/mTOR kinase cascade mediate intrinsic resistance to BET inhibitors in Ewing sarcoma.
Repression of autocrine IGF1 by BET inhibitors led to significant inhibition of the IGF1R/AKT pathway critical to Ewing sarcoma cell proliferation and survival.
Molecular examination reveals that the action of ezrin in Ewing's sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase.