{"doi":"10.17161/sjm.v2i4.24269","title":"FOXA2 and NKX2-1 Orchestrate Neuroendocrine Lineage Plasticity in Prostate Cancer","abstract":"Neuroendocrine prostate cancer (NEPC) is a treatment-resistant subtype that arises through lineage plasticity, allowing tumor cells to bypass androgen receptor (AR)–targeted therapies. In a recent study, Lu et al. define a transcriptional and epigenetic hierarchy that drives this transdifferentiation. The pioneer factor FOXA2 initiates enhancer remodeling and regional DNA demethylation, while the neural lineage transcription factor NKX2-1 is required to complete the NE program. Together, these factors reorganize 3D chromatin architecture and activate lineage-specific genes through enhancer–promoter looping. Crucially, the histone acetyltransferase p300/CBP is essential cofactor in this process. Pharmacologic inhibition of p300/CBP with CCS1477 suppresses NE gene expression and impairs tumor growth in NEPC models. These findings offer a mechanistic insight of lineage plasticity and highlight p300/CBP as promising therapeutic targets. The study also raises key questions about the stability and reversibility of chromatin remodeling and sets a framework for understanding enhancer-driven plasticity in other cancers.","journal":"Serican Journal of Medicine","year":2025,"id":576638,"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":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":817996,"name":"Ka-wing Fong","orcid":"0000-0001-6995-0264","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:00.620755Z","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":[]}