Synthetic Lethal Metabolic Targeting of Senescent Cells after Androgen Deprivation Therapy

Abstract

Progression to castrate resistant prostate cancer for men with advanced prostate cancer(PC) results after the initiation of androgen deprivation therapy (ADT). One underutilized strategy that has the potential to dramatically improve outcomes is eradicating persistent senescent cancer cells that remain after ADT and likely play a key role in castration-resistant PC. We have demonstrated that ADT induces senescence in androgen-dependent PC cells and acts synergistically with the diabetes medication metformin to induce apoptosis in PC cells. We have also shown that metformin enhances the antitumor activity of ADT in a murine PDX PC model. Analysis of the VA database revealed that metformin use in patients with advanced prostate cancer receiving ADT is associated with improved OS and cancer-specific survival. Our results point to metformin as a novel therapeutic strategy for castration-resistant PC.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2018
Accession Number
AD1057805

Entities

People

  • Vincent Cryns

Organizations

  • University of Wisconsin System

Tags

DTIC Thesaurus Topics

  • Agent Orange
  • Biological Sciences
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Clinical Trials
  • Data Analysis
  • Databases
  • Department Of Veterans Affairs
  • Diseases And Disorders
  • Health Services
  • Hormones
  • Medical Personnel
  • Neoplasms
  • Oncology
  • Prostate
  • Prostate Cancer
  • Resistance
  • Side Effects
  • Stress (Physiology)
  • Therapy
  • Tissues
  • Toxicity
  • United States

Fields of Study

  • Biology

Readers

  • Prostate Cancer Biology.