Khanh Do, MD
Dana-Farber Cancer Institute

The newly formed proteins that execute many of the cancer-growing activities in solid tumors (such as increasing the blood supply, resisting normal cell death signals, metastasis, etc.) require “housekeeping” support. Housekeeping proteins help the cancer proteins to fold properly so they can turn on and achieve stability.

These researchers are targeting a main housekeeping protein, Hsp90, and an ancillary housekeeping protein, Hsp70, with a dual approach. By combining therapies to block these proteins, it is hoped that many of the cancer proteins will be unable to function.

The aim of this study is to acquire the information necessary to design and execute a larger combination study that will target multiple cancer-causing and resistance pathways for advanced cancer patients for whom curative or palliative measures do not exist or are no longer effective. [Awarded 2015]

 

Clinical Summary
Inhibition of the 90kDa heat shock protein (Hsp90) holds the potential for simultaneous blockade of multiple pathways responsible for the hallmarks of cancer (angiogenesis, growth advantage, avoidance of cell death, metastasis, etc.) as the proteins central to these processes all depend upon Hsp90 chaperone function and protection. Maximal response to Hsp90 inhibition may be hampered by a compensatory response of other heat shock proteins, especially Hsp70. Inhibition of the production of Hsp70 (through inhibition of CDK) may improve response to Hsp90 inhibition. Dr. Do proposes that dual inhibition of CDK and Hsp90 activity through co-administration of AT13387 and AT7519 presents a novel opportunity to enhance the therapeutics of these classes of agents through parallel targeting of resistance pathways and allow concurrent targeting of simultaneous oncogenic pathways. The ultimate aim of this study is the development of the combination study that will allow for the simultaneous targeting of multiple oncogenic and resistance pathways in order to achieve a meaningful palliation for advanced cancer patients for whom curative/palliative measures do not exist or are no longer effective. [Awarded 2015]