Autophagy Inhibition for Chemosensitization and Radiosensitization in Cancer: Do the Preclinical Data Support This Therapeutic Strategy?

• DOI: 10.1124/jpet.112.199802
• Publication Date: 2013-01-05T05:01:47Z
• Authors: Molly L. Bristol; Sean M. Emery; Paola Maycotte; Andrew Thorburn; Shweta Chakradeo; David A. Gewirtz
• Keywords: Hydroxychloroquine

Recognition of the cytoprotective functions autophagy that occur in tumor cells exposed to various forms chemotherapy or radiation has generated intense interest possibility pharmacological interference with could provide a clinical strategy for overcoming therapeutic resistance. Multiple trials are currently progress evaluate antimalarial agent chloroquine (generally its formulation as hydroxychloroquine) and impact on cancer therapy. In this commentary/review, we focus relatively limited number studies literature where been tested combination experimental tumor-bearing animal models. We also present recent data from our own laboratories, cell culture experiments well vivo studies, which demonstrate neither nor silencing an regulatory gene was effective conferring sensitivity model breast cancer. The capacity sensitization by appears be quite wide-ranging, dramatic effects some drugs/tumor models modest minimal others. One possible caveat is that, only few exceptions, have generally performed xenograft models, thereby eliminating involvement immune system, might ultimately proven play central role determining effectiveness inhibition chemosensitization radiosensitization. Nevertheless, careful review current suggests caution likely warranted translating preclinical findings relating adjunctive strategy.