{"doi":"10.1016/j.celrep.2022.111123","title":"Dynamic plasticity of prostate cancer intermediate cells during androgen receptor-targeted therapy","abstract":"Treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC) is associated with an epithelial lineage switch from an androgen receptor (AR)-positive to neuroendocrine (NE)-marker-positive status. Understanding the potential for reversibility of this aggressive disease state has been hampered by the paucity of models suitable for studying rate-limiting, transitional, or intermediate tumor cell subpopulations. We define a dual reporter model that measures acute transcriptional changes in response to castration or AR targeting agents. We identify steady-state transcriptional heterogeneity in AR and NE biomarkers, including intermediate subpopulations that are coordinately high for prostate-specific antigen (PSA) and neuron-specific enoclase (NSE) promoter activity. In the presence of castration or AR inhibitors, intermediate cells were necessary and sufficient for therapy-induced conversion of human PC cells to an NSE-high transcriptional status. Using hormone add-back studies, treatment-induced PSA-NSE transcriptional plasticity was reversible in PTEN-deficient PC cells but not in the presence of secondary genetic driver genes, including MYCN.","journal":"Cell Reports","year":2022,"id":243134,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":875529,"name":"Kensey Portman","orcid":null,"position":1,"is_corresponding":false},{"id":4390,"name":"Xianxiao Zhou","orcid":"0000-0001-9350-4467","position":2,"is_corresponding":false},{"id":329944,"name":"Julia N. Zhao","orcid":"0000-0002-4352-7748","position":3,"is_corresponding":false},{"id":245653,"name":"Alexander Rialdi","orcid":"0000-0001-5393-9247","position":4,"is_corresponding":false},{"id":274818,"name":"John P. Sfakianos","orcid":"0000-0002-3101-0266","position":5,"is_corresponding":false},{"id":23521,"name":"Ernesto Guccione","orcid":"0000-0001-7764-5307","position":6,"is_corresponding":false},{"id":264835,"name":"Natasha Kyprianou","orcid":"0000-0002-8713-3599","position":7,"is_corresponding":false},{"id":107090,"name":"Bin Zhang","orcid":"0000-0002-9549-5653","position":8,"is_corresponding":false},{"id":654728,"name":"David J. Mulholland","orcid":"0000-0002-6061-7382","position":9,"is_corresponding":false},{"id":874843,"name":"Harkirat Singh Sandhu","orcid":"0000-0002-4664-2039","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"35905714","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":[]}