Developing Strategies to Overcome Prostate Stromal-Derived NRG1-Mediated Resistance to AR Blockade in High-Risk Locally Advanced Prostate Cancer
Abstract
Through pre-clinical studies, we have recently discovered for the first time, that the prostate cancer microenvironment stromal cells, secrete neuregulin (NRG1) in response to androgen blockade, which promotes the cancer cells to survival an androgen deprived state. Our recent finding explains in part why, so few high-risk primary prostate cancers achieve a complete pathologic response to androgen blockade. Importantly, the neuregulin signaling pathway is therapeutically actionable with several clinical agents either FDA approved for other malignancies or in early development. Our research proposal aims to define the downstream mechanisms through which NRG1 promotes cell survival and determine the therapeutic strategies targeting the NRG1 pathway which enhance response to androgen blockade. Our work has the potential to improve our understanding of how the cancer environment influences resistance to androgen blockade and lead to novel combination therapies vastly changing the standard of care for men with high-risk prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1205238
Entities
People
- Brett S. Carver
Organizations
- Memorial Sloan Kettering Cancer Center