The Role of Ubiquitination in CRPC Transitioning to NEPC
Abstract
Recent advances in treating castration-resistant prostate cancers using next-generation androgen receptor pathway inhibitors (i.e., abiraterone and enzalutamide) efficiently inactivate androgen receptor signaling. However, castration-resistant prostate cancer patients rapidly become resistant to androgen receptor pathway inhibitors. About 20% of these patients develop a highly aggressive neuroendocrine prostate cancer. Currently, no target therapy is available for neuroendocrine prostate cancer. Understanding the molecular mechanisms driving castration-resistant prostate cancer to become neuroendocrine prostate cancer would provide valuable insights into the development of target therapies. We recently found that an oncogenic enzyme, TRAF4, is important for castration-resistant prostate cancer development. It is also gene amplified in 25% of neuroendocrine prostate cancer patients. The goal of this proposed research is to understand the role of TRAF4 in neuroendocrine prostate cancer development. We will also test the effect of a potential TRAF4 enzyme inhibitor on controlling castration-resistant prostate cancer progression to neuroendocrine prostate cancer. Completion of this proposal will provide a novel therapeutic strategy to prevent next-generation androgen pathway inhibitor-resistant patients with high TRAF4 expression from developing neuroendocrine prostate cancer. If successful, it will decrease the death from TRAF4-overexpressing prostate cancers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110404
Entities
People
- Ping Yi
Organizations
- Baylor College of Medicine
- United States Army