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Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes.
Venkadakrishnan, Varadha Balaji; Presser, Adam G; Singh, Richa; Booker, Matthew A; Traphagen, Nicole A; Weng, Kenny; Voss, Nathaniel C E; Mahadevan, Navin R; Mizuno, Kei; Puca, Loredana; Idahor, Osasenaga; Ku, Sheng-Yu; Bakht, Martin K; Borah, Ashir A; Herbert, Zachary T; Tolstorukov, Michael Y; Barbie, David A; Rickman, David S; Brown, Myles; Beltran, Himisha.
Afiliação
  • Venkadakrishnan VB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Presser AG; Harvard Medical School, Boston, MA, USA.
  • Singh R; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Booker MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Traphagen NA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Weng K; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Voss NCE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Mahadevan NR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Mizuno K; Boston College, Chestnut Hill, MA, USA.
  • Puca L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Idahor O; Belmont Hill School, Belmont, MA, USA.
  • Ku SY; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Bakht MK; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Borah AA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Herbert ZT; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • Tolstorukov MY; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Barbie DA; Harvard University, Cambridge, MA, USA.
  • Rickman DS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Brown M; Harvard Medical School, Boston, MA, USA.
  • Beltran H; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Commun ; 15(1): 6779, 2024 Aug 08.
Article em En | MEDLINE | ID: mdl-39117665
ABSTRACT
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs in NEPC, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação Neoplásica da Expressão Gênica / Proteína Potenciadora do Homólogo 2 de Zeste Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação Neoplásica da Expressão Gênica / Proteína Potenciadora do Homólogo 2 de Zeste Idioma: En Ano de publicação: 2024 Tipo de documento: Article