Given that AKT activation and expression of P-EphA2S897 are prevalent events in primary and recurrent GBM [10], [47], [48], and our data implicating LRP1 upregulation in clinical specimens, a model is proposed whereby GBM tumors amplify both eHsp90-LRP1 and AKT-EphA2 signaling axes to create a synergistic feed forward circuit that supports GBM aggressiveness. Here, EPHA2 is linked to glioblastoma.