{"doi":"10.3410/f.736662069.793573886","title":"Faculty Opinions recommendation of Enzalutamide Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors.","abstract":"The second-generation anti-androgen, enzalutamide (ENZ), is approved for castrate-resistant (CR) PC and targets androgen receptor (AR) activity in CRPC. Despite initial clinical activity, acquired resistance to ENZ arises rapidly and most patients develop terminal disease. Previous work has established Stat5 as a potent inducer of PC growth. Here, we investigated the significance of Jak2-Stat5 signaling in resistance of PC to ENZ. The levels of Jak2 and Stat5 mRNA, proteins and activation were evaluated in PC cells, xenograft tumors and clinical PCs before and after ENZ therapy. Jak2 and Stat5 were suppressed by genetic knockdown using lentiviral shRNA or pharmacological inhibitors. Responsiveness of primary and ENZ resistant PC to pharmacological inhibitors of Jak2-Stat5 signaling was assessed in vivo in mice bearing PC xenograft tumors. Patient-derived PCs were tested for responsiveness to Stat5 blockade as second line treatment after ENZ ex vivo in tumor explant cultures. ENZ-liganded AR induces sustained Jak2-Stat5 phosphorylation in PC leading to a formation of a positive feed-forward loop, where activated","journal":"Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature","year":2020,"id":134525,"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":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":590152,"name":"Brion W. Murray","orcid":"0000-0003-1591-2566","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:16:24.540681Z","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":[]}