Targeting GPR30 in Abiraterone and MDV3100-Resistant Prostate Cancer
Abstract
New treatments to abiraterone (Abi)- and MDV3100 (MDV)-resistant prostate cancer have not been explored. G protein-coupled receptor 30 (GPR30) is a seven-transmembrane estrogen receptor and the activation by its specific agonist G-1 inhibited growth in multiple castration-resistant prostate cancer (CRPC) xenograft models that were resistant to the first-generation androgen deprivation therapy (ADT). More importantly, GPR30 is an androgen-repressed target and its expression increased in clinical CRPC when compared to primary prostate cancer. In this proposal, we will conduct preclinical studies to test the efficacy of G-1 in inhibiting the growth of prostate cancer that are resistant to the new second-generation ADT including Abi and MDV. We characterized two patient-derived xenograft models that are resistant to Abi and MDV, and the efficacy study of G-1 in inhibiting tumor growth are undergoing. We are also collecting clinical Abi- and MDV-resistant prostate cancer specimens from both biopsy and rapid autopsy to evaluate the prevalence of GPR30 expression in these advanced patients for potential targeting. This study will also provide information on the mechanism underlying GPR30 responsiveness and resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1007733
Entities
People
- Hung-ming Lam
Organizations
- University of Washington