Targeting GPR30 in Abiraterone and MDV3100-Resistant Prostate Cancer
Technical Report,30 Sep 2014,29 Sep 2015
University of Washington Seattle United States
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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.