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Development of Molecular Chaperone Inhibitors for (Re) Sensitization of CRPC to Enzalutamide and Abiraterone and to Synergize with Metabolic Inhibitors

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[Technical Report, Annual Report]

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Objective 1 Improve the solubility and pharmacodynamic properties of previously identified Hsp40 and Hsp70 inhibitors in preparation for Phase I clinical evaluation in CRPC patients. 2 Determine whether these chaperone inhibitors sensitize resistant CRPC to Enz andor Abi and, if so, by what mechanisms. 3 Increase our understanding of the role of these chaperones in regulating CRPC metabolic deregulation, with the goal of identifying novel synergistic combinatorial approaches to target CRPC. Impact By identifying a chaperone-based approach to inhibit or reverse CRPC resistance to Enz andor Abi, the current research proposal addresses the dual 2018 PCRP Overarching Challenges of 1 developing treatments that improve the outcomes for men with lethal prostate cancer and 2 better defining the biology of lethal prostate cancer to reduce death. Further, consistent with the mandate of the PCRP Impact Award, a key goal of our research strategy is to position the program for first-in-human clinical evaluation of one or more of these chaperone inhibitors within 5 years after completion of this Award.


Subject Categories:

  • Medicine and Medical Research
  • Pharmacology

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[A, Approved For Public Release]