Therapeutic Targeting of Neuroendocrine Prostate Cancer

Abstract

Increased incidence of treatment induced neuroendocrine prostate cancer (NEPC) is particularly alarming as this diagnosis is associated with poor prognosis and decades of cytotoxic chemotherapy as the only treatment option. We previously identified neuronal transcription factor BRN2 as a potent driver of neuroendocrine differentiation and an attractive target in NEPC. Our goal is to Evaluate the mechanism by which BRN2 alters chromatin architecture to support neuroendocrine lineage reprogramming. We used unbiased approach to identify BRN2 cofactors using both in house and publicly available BRN2 ChIPseq and Rapid immunoprecipitation mass spectrometry. Our research demonstrates that BRN2 regulates chromatin organization/remodeling, pre-mRNA splicing, and cell cycle progression (especially at the G2-M checkpoint and during mitosis) through direct interactions with important factors involved in these processes and also through transcriptional regulation of the expression of such factors. Importantly, task that we were planning to achieved were setback because of the COVID restriction that were imposed by our Canadian government and the University of British Columbia. We applied and received an extension to complete our proposed tasks.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2021
Accession Number
AD1149969

Entities

People

  • Amina Zoubeidi

Organizations

  • University of British Columbia
  • University of Washington

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Apoptosis
  • Biomedical Research
  • British Columbia
  • Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Department Of Defense
  • Gene Expression
  • Genetic Phenomena
  • Genetic Structures
  • Genetics
  • Inhibitors
  • Lung Cancer
  • Maryland
  • Mass Spectrometry
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Small Molecules
  • Targeting
  • Transcription Factors
  • Universities

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and Cellular Biology
  • Oncology (Cancer Research).