{"doi":"10.1002/cpz1.742","title":"Preclinical Models of Neuroendocrine Prostate Cancer","abstract":"<jats:title>Abstract</jats:title><jats:p>Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer‐related death amongst men in the United States. Neuroendocrine prostate cancer (NEPC) can either arise <jats:italic>de novo</jats:italic> or emerge as a consequence of therapy. <jats:italic>De novo</jats:italic> NEPC is rare, with an incidence of &lt;2% of all PCa cases. In contrast, treatment‐induced NEPC is frequent with &gt;20% of patients with metastatic castration‐resistant prostate cancer (CRPC) reported to progress to neuroendocrine (NE) differentiation. The emergence of treatment‐induced NEPC is linked to the increased therapeutic pressure, due to the broad application of androgen deprivation therapy (ADT) for PCa management and the development of novel more potent androgen receptor (AR) pathway inhibitors. NEPC is a high‐grade tumor type characterized by aggressive phenotype and clinical behavior. Patients affected by NEPC frequently develop visceral metastases and have a poor prognosis. The molecular mechanisms underlying the development and progression of NEPC are still poorly understood. Transcriptional and epigenetic reprogramming appears to be involved in NE progression. In this review, we aim to provide a comprehensive view of the available models for NEPC detailing their strengths and limitations. Moreover, we describe novel approaches to expand the repertoire of preclinical models to better study, prevent, or reverse NEPC. The integration of multiple preclinical models along with molecular and omics approaches will provide important insights to understand disease progression and to devise novel therapeutic strategies for the management of NEPC in the near future. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.</jats:p><jats:p><jats:bold>Basic Protocol 1</jats:bold>: Generation of organoids starting from the prostate gland of a GEMM or a human PDX</jats:p><jats:p><jats:bold>Basic Protocol 2</jats:bold>: <jats:italic>Ex vivo</jats:italic> tumor sphere formation</jats:p>","journal":"Current Protocols","year":2023,"id":609272,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":564815,"name":"Domenico Albino","orcid":"0000-0001-6249-4163","position":1,"is_corresponding":false},{"id":589333,"name":"Carlo V. Catapano","orcid":"0000-0002-7079-557X","position":2,"is_corresponding":false},{"id":564819,"name":"Giuseppina M. Carbone","orcid":"0000-0003-4652-585X","position":3,"is_corresponding":false},{"id":1565909,"name":"Alessia Cacciatore","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Preclinical Models of Neuroendocrine Prostate Cancer","abstract":"<jats:title>Abstract</jats:title><jats:p>Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer‐related death amongst men in the United States. Neuroendocrine prostate cancer (NEPC) can either arise <jats:italic>de novo</jats:italic> or emerge as a consequence of therapy. <jats:italic>De novo</jats:italic> NEPC is rare, with an incidence of &lt;2% of all PCa cases. In contrast, treatment‐induced NEPC is frequent with &gt;20% of patients with metastatic castration‐resistant prostate cancer (CRPC) reported to progress to neuroendocrine (NE) differentiation. The emergence of treatment‐induced NEPC is linked to the increased therapeutic pressure, due to the broad application of androgen deprivation therapy (ADT) for PCa management and the development of novel more potent androgen receptor (AR) pathway inhibitors. NEPC is a high‐grade tumor type characterized by aggressive phenotype and clinical behavior. Patients affected by NEPC frequently develop visceral metastases and have a poor prognosis. The molecular mechanisms underlying the development and progression of NEPC are still poorly understood. Transcriptional and epigenetic reprogramming appears to be involved in NE progression. In this review, we aim to provide a comprehensive view of the available models for NEPC detailing their strengths and limitations. Moreover, we describe novel approaches to expand the repertoire of preclinical models to better study, prevent, or reverse NEPC. The integration of multiple preclinical models along with molecular and omics approaches will provide important insights to understand disease progression and to devise novel therapeutic strategies for the management of NEPC in the near future. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.</jats:p><jats:p><jats:bold>Basic Protocol 1</jats:bold>: Generation of organoids starting from the prostate gland of a GEMM or a human PDX</jats:p><jats:p><jats:bold>Basic Protocol 2</jats:bold>: <jats:italic>Ex vivo</jats:italic> tumor sphere formation</jats:p>","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37166213","pmcid":null,"openalex_id":"https://openalex.org/W4376130924","authors":[],"funders":[{"funder_name":"Foundation Nelia et Amadeo Barletta","grant_id":"","title":null},{"funder_name":"Fondazione San Salvatore","grant_id":"","title":null},{"funder_name":"Fondazione Ticinese Ricerca sul Cancro","grant_id":"","title":null}],"total_grants":3,"fwci":3.0092,"citation_percentile":0.92410729,"influential_citations":0,"citation_trend":[{"year":2023,"count":2},{"year":2024,"count":5},{"year":2025,"count":7},{"year":2026,"count":4}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpz1.742","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cpz1.742","host_type":"publisher"},{"url":"https://currentprotocols.onlinelibrary.wiley.com/doi/pdf/10.1002/cpz1.742","host_type":"publisher"},{"url":"https://doi.org/10.1002/cpz1.742","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37166213","host_type":"repository"}],"fields_of_study":["Prostate Cancer Treatment and Research","Estrogen and related hormone effects","Receptor Mechanisms and Signaling"],"mesh_terms":["Androgen Antagonists","Humans","Male","Prostate","Prostatic Neoplasms","Androgen Receptor Antagonists"],"keywords":["Prostate cancer","Medicine","Oncology","Internal medicine","Cancer","Preclinical Models","Genetically Engineered Mouse Model (Gemm)","Patient-derived Xenografts (Pdx)","Neuroendocrine Prostate Cancer (Nepc)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T05:22:59.921907Z","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":[]}