Cotargeting the Trinity of DNA Damage Repair Sensing Kinases in Prostate Cancer

Abstract

In this grant, we will systematically establish the preclinical utility of Compound B for clinical translation as combination therapy with cytotoxic therapies. Specifically, we will: Specific Aim 1: Characterize effects of RUVBL1/2 inhibition on DNA damage repair and induction of apoptosis in prostate cancer cells in vitro and patient derived explants ex vivo; Specific Aim 2: Evaluate the therapeutic efficacy of combining RUVBL1/2 inhibition with ionizing radiation on DNA damage repair and cell survival of prostate cancer xenografts in vivo; Specific Aim 3: Characterize immunostimulatory effects of RUVBL1/2 inhibition in prostate cancer cells in vitro, ex vivo and in vivo using immuncompetent syngeneic tumor models. We expect that our data will establish the preclinical rationale for developing clinical trials with RUVBL1/2 inhibitors in prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2022
Accession Number
AD1191053

Entities

People

  • Ganesh V Raj

Organizations

  • University of Texas at Austin

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Anatomy
  • Apoptosis
  • Biological Sciences
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Clinical Trials
  • Combination Therapy
  • Department Of Defense
  • Information Operations
  • Inhibition
  • Inhibitors
  • Ionizing Radiation
  • Maryland
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Radiation
  • Therapy
  • Xenografts

Fields of Study

  • Biology
  • Medicine

Readers

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  • Oncology
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