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Synapse
May 31, 2026Open Access

A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.

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Authors

FAFrancisca Nunes de AlmeidaAVAlessandro VasciaveoAGArianna Giacobbe

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Overview

Randomized trial identifies SIRT1 promoting neuroendocrine prostate cancer, suggesting new treatment pathways.

Key Points

  • To identify genetic drivers of aggressive neuroendocrine prostate cancer using forward genetic screening.
  • Utilized Sleeping Beauty transposon mutagenesis in mouse models (NPp53 mice) to induce tumorigenesis.
  • Compared experimental NPp53-SB(+) mice and control NPp53-SB(-) mice to assess tumor aggressiveness and metastasis.
  • Conducted gain- and loss-of-function studies in human prostate cancer cells and mouse NEPC organoids.
  • NPp53-SB(+) mice developed aggressive tumors with increased metastasis compared to NPp53-SB(-) mice.
  • Transcriptomic analysis prioritized SIRT1 as a key driver in NEPC, showing significant differential expression between NEPC and non-NEPC tumors.
  • Pharmacological inhibition of SIRT1 suppressed NEPC progression in experimental models.

Cite This Study

Almeida et al. (2026) studied this question.

synapsesocial.com/papers/6a1bd0845783ba022b6fc406https://doi.org/10.48620/98221
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer2024
  2. 2A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer2026
  3. 3Epigenetic De-repression of PROX1 Promotes Neuroendocrine Prostate Cancer Progression2025 · 6 citations
  4. 4Distinct neuroendocrine subtypes predict treatment-induced neuroendocrine prostate cancer prognosis and provide clues for personalized treatment2024
  5. 5Data from Epigenetic Derepression of PROX1 Promotes Neuroendocrine Prostate Cancer Progression2025 · 1 citations