{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":45,"searchCount":0},"additional":{"submitter":["Liu C"],"funding":["BLRD VA","United States Department of Defense | United States Army | US Army Corps of Engineers | Engineer Research and Development Center","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","U.S. Department of Veterans Affairs"],"pagination":["5379-5392"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8413131"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["40(35)"],"pubmed_abstract":["Targeting androgen signaling with the second-generation anti-androgen drugs, such as enzalutamide (Enza), abiraterone (Abi), apalutamide (Apal), and darolutamide (Daro), is the mainstay for the treatment of castration-resistant prostate cancer (CRPC). While these treatments are effective initially, resistance occurs frequently. Continued expression of androgen receptor (AR) and its variants such as AR-V7 despite AR-targeted therapy contributes to treatment resistance and cancer progression in advanced CRPC patients. This highlights the need for new strategies blocking continued AR signaling. Here, we identify a novel AR/AR-V7 degrader (ARVib) and found that ARVib effectively degrades AR/AR-V7 protein and attenuates AR/AR-V7 downstream target gene expression in prostate cancer cells. Mechanistically, ARVib degrades AR/AR-V7 protein through the ubiquitin-proteasome pathway mediated by HSP70/STUB1 machinery modulation. ARVib suppresses HSP70 expression and promotes STUB1 nuclear translocation, where STUB1 binds to AR/AR-V7 and promotes its ubiquitination and degradation. ARVib significantly inhibits resistant prostate tumor growth and improves enzalutamide treatment in vitro and in vivo. These data suggest that ARVib has potential for development as an AR/AR-V7 degrader to treat resistant CRPC."],"journal":["Oncogene"],"pubmed_title":["ARVib suppresses growth of advanced prostate cancer via inhibition of androgen receptor signaling."],"pmcid":["PMC8413131"],"funding_grant_id":["IK6BX005222","R01 CA225836","I01BX0002653","CA225836","R01 CA253605","R01 CA251253","R37 CA249108","IK6 BX005222","R43 CA206668","R01 CA250082","DOD PC150229","R01 CA168601","I01 BX004036","P30 CA093373"],"pubmed_authors":["Evans CP","Tepper CG","Li PK","Lombard AP","Wu CY","Lou W","Ning S","Yang JC","Yu A","Liu C","Armstrong CM","Gao AC","Zhao J"],"view_count":["45"],"additional_accession":[]},"is_claimable":false,"name":"ARVib suppresses growth of advanced prostate cancer via inhibition of androgen receptor signaling.","description":"Targeting androgen signaling with the second-generation anti-androgen drugs, such as enzalutamide (Enza), abiraterone (Abi), apalutamide (Apal), and darolutamide (Daro), is the mainstay for the treatment of castration-resistant prostate cancer (CRPC). While these treatments are effective initially, resistance occurs frequently. Continued expression of androgen receptor (AR) and its variants such as AR-V7 despite AR-targeted therapy contributes to treatment resistance and cancer progression in advanced CRPC patients. This highlights the need for new strategies blocking continued AR signaling. Here, we identify a novel AR/AR-V7 degrader (ARVib) and found that ARVib effectively degrades AR/AR-V7 protein and attenuates AR/AR-V7 downstream target gene expression in prostate cancer cells. Mechanistically, ARVib degrades AR/AR-V7 protein through the ubiquitin-proteasome pathway mediated by HSP70/STUB1 machinery modulation. ARVib suppresses HSP70 expression and promotes STUB1 nuclear translocation, where STUB1 binds to AR/AR-V7 and promotes its ubiquitination and degradation. ARVib significantly inhibits resistant prostate tumor growth and improves enzalutamide treatment in vitro and in vivo. These data suggest that ARVib has potential for development as an AR/AR-V7 degrader to treat resistant CRPC.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2024-11-14T18:32:23.637Z","creation":"2022-02-11T16:20:00.732Z"},"accession":"S-EPMC8413131","cross_references":{"pubmed":["34272475"],"doi":["10.1038/s41388-021-01914-2"]}}