Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma

In this study, we evaluated Hsp90 as a potential therapeutic target in BL. We found that primary BL tumors overexpress Hsp90 and that Hsp90 inhibition has antitumor activity in vitro and in vivo, including potent activity in a patient-derived xenograft model of BL. To evaluate the targets of PU-H71 in BL, we performed high-affinity capture followed by proteomic analysis using mass spectrometry. We found that Hsp90 inhibition targets multiple components of PI3K/AKT/mTOR signaling, highlighting the importance of this pathway in BL. Finally, we found that the anti-lymphoma activity of PU-H71 is synergistic with dual PI3K/mTOR inhibition in vitro and in vivo. Overall, this work provides support for Hsp90 as a therapeutic target in BL and suggests the potential for combination therapy with PU-H71 and inhibitors of PI3K/mTOR. Mol Cancer Ther; 16(9); 1779–90. ©2017 AACR.

Source: Molecular Cancer Therapeutics - September 4, 2017 Category: Cancer & Oncology Authors: Giulino-Roth, L., van Besien, H. J., Dalton, T., Totonchy, J. E., Rodina, A., Taldone, T., Bolaender, A., Erdjument-Bromage, H., Sadek, J., Chadburn, A., Barth, M. J., Dela Cruz, F. S., Rainey, A., Kung, A. L., Chiosis, G., Cesarman, E. Tags: Small Molecule Therapeutics Source Type: research