{"doi":"10.1158/1078-0432.c.6516892","title":"Data from Bortezomib-Mediated Inhibition of Steroid Receptor Coactivator-3 Degradation Leads to Activated Akt","abstract":"<div>Abstract<p><b>Purpose:</b> To assess the safety of administering bortezomib to patients undergoing a radical prostatectomy, to assess pathologic changes induced by bortezomib in prostate cancer specimen, and to verify alterations by the drug in proteasome protein targets.</p><p><b>Experimental Design:</b> Bortezomib is a proteasome inhibitor that has shown activity <i>in vitro</i> and <i>in vivo</i> in prostate cancer. We performed a neoadjuvant clinical trial of bortezomib in men with prostate cancer at high risk of recurrence. The primary endpoints were to evaluate safety and biological activity.</p><p><b>Results:</b> Bortezomib is generally safe in the preoperative setting. Antitumor activity was manifested by tumor cytopathic effect, drops in serum prostate-specific antigen in some patients, and increases in tumor apoptosis. This was associated with cytoplasmic entrapment of nuclear factor-κB. We found an unexpected increase in proliferation in treated tissues and <i>in vitro</i>. Bortezomib also increased SRC-3 levels and phosphorylated Akt, both <i>in vitro</i> and in treated prostate cancer tissues. Knockdown of SRC-3 blocked the increase in activated Akt <i>in vitro</i>. Combined treatment with bortezomib and the Akt inhibitor perifosine was more effective than either agent alone <i>in vitro</i>.</p><p><b>Conclusion:</b> These data suggest that combined therapies targeting the proteasome and the Akt pathway may have increased efficacy.</p></div>","journal":null,"year":2023,"id":405075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9395,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250194,"name":"Jun Yan","orcid":"0000-0003-2922-422X","position":1,"is_corresponding":false},{"id":1183740,"name":"Rile Li","orcid":null,"position":2,"is_corresponding":false},{"id":548313,"name":"Yi Ding","orcid":"0000-0002-1498-7155","position":3,"is_corresponding":false},{"id":261734,"name":"Timothy C. Thompson","orcid":"0000-0003-1424-3831","position":4,"is_corresponding":false},{"id":997880,"name":"Martha P. Mims","orcid":null,"position":5,"is_corresponding":false},{"id":1183741,"name":"Teresa G. Hayes","orcid":null,"position":6,"is_corresponding":false},{"id":1183742,"name":"Vivian MacDonnell","orcid":null,"position":7,"is_corresponding":false},{"id":1183743,"name":"R. Garret Lynch","orcid":null,"position":8,"is_corresponding":false},{"id":1183378,"name":"Anna Frolov","orcid":"0000-0002-7617-7852","position":9,"is_corresponding":false},{"id":336722,"name":"Brian J. Miles","orcid":"0000-0001-7927-9873","position":10,"is_corresponding":false},{"id":582216,"name":"Thomas M. Wheeler","orcid":"0000-0001-9746-1521","position":11,"is_corresponding":false},{"id":242348,"name":"J. Wade Harper","orcid":"0000-0002-6944-7236","position":12,"is_corresponding":false},{"id":245524,"name":"Ming‐Jer Tsai","orcid":"0000-0001-6287-908X","position":13,"is_corresponding":false},{"id":13598,"name":"Michael Ittmann","orcid":"0000-0003-4802-0978","position":14,"is_corresponding":false},{"id":1183744,"name":"Dov Kadmon","orcid":null,"position":15,"is_corresponding":false},{"id":336723,"name":"Gustavo Ayala","orcid":"0000-0002-5288-0244","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T01:20:49.237119Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}