Development of Molecular Chaperone Inhibitors for (Re)Sensitization of CRPC to Enzalutamide and Abiraterone and to Synergize with Metabolic Inhibitors
Abstract
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 and/or Abi and, if so, by what mechanism(s). (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 and/or 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 5years after completion of this Award.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1220641
Entities
People
- Leonard Neckers
Organizations
- Geneva Foundation