Mp20-07 nptx1 Is a Novel Serum Biomarker Induced by Arpi Treated Prostate Cancer and Enriched in Lineage Plasticity With Brn2 High

Namekawa, Takeshi; Scurll, Joshua M; Kobelev, Maxim; Ganguli, Dwaipayan; Sivak, Olena; Gleave, Martin; Vancouver,; Canada, .; Corey, Eva; Morrissey, Colm; Zoubeidi, Amina

doi:10.1097/ju.0000000000003245.07

Cited by 2 publications

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“…EZH2 inhibition also led to an increase in expression of NElineage transcription factors in other NEPC models WCM155 and WCM1262 (SFig 4C). Of note, several NE-lineage adhesion or secreted proteins, including DLL3, NPTX1, NRXN2, NTRK2, NRP2 were upregulated upon EZH2 inhibition in NEPC models and portrayed bivalency in their promoters (SFig 4D-E) (29,30).…”

Section: Induction Of Ne-lineage Genes Upon Ezh2 Inhibition Contribut...mentioning

confidence: 99%

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Venkadakrishnan,

Presser,

Singh

et al. 2024

Preprint

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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 (PRAD) 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), neuronal gene programs, and 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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Section: Induction Of Ne-lineage Genes Upon Ezh2 Inhibition Contribut...mentioning

confidence: 99%

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Venkadakrishnan,

Presser,

Singh

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Venkadakrishnan,

Presser,

Singh

et al. 2024

Nat Commun

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Mp20-07 nptx1 Is a Novel Serum Biomarker Induced by Arpi Treated Prostate Cancer and Enriched in Lineage Plasticity With Brn2 High

Abstract: cancer. LPHNs could thus be independent prognosticators in prostate cancer patients undergoing radical prostatectomy, as well as therapeutic targets for both androgen-sensitive and castration-resistant tumors.

Cited by 2 publications

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Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes

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