Overcoming Autophagy to Induce Apoptosis in Castration-Resistant Prostate Cancer

Abstract

With the approval of the next generation anti-androgens such as enzalutamide and abiraterone (Abi) for advanced prostate cancer therapy, we attempted to evaluate whether combination of anti-androgen abiraterone and autophagy modulator metformin might block progression to castration resistant prostate cancer using the CWR22 xenograft model. CWR22 xenograft is considered the tumor model that may reprise tumor progression in patients under androgen deprivation therapy (ADT). CWR22 tumors normally reach around 100 mm3 in size in nude mice implanted with testosterone pellets in one month of time. After castration, tumors regress due to the decline of androgen and remain dormant for a length of time varying from 3 to 5 months. After that, tumors relapse and continue to grow vigorously independent of further ADT. However, due to the contamination of the frozen CWR22 samples used for tumor implantation, the assumed CWR22 tumors continued to grow after castration and were not inhibited by abiraterone, metformin and the combination.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2016
Accession Number
AD1030560

Entities

People

  • Christopher P Evans

Organizations

  • University of California, Davis

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Antidepressants
  • Apoptosis
  • Autophagy
  • Castration
  • Cell Line
  • Cell Physiological Processes
  • Deprivation
  • Diseases And Disorders
  • Gene Expression
  • Modulators
  • Molecules
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Stress (Physiology)

Fields of Study

  • Biology

Readers

  • Military History of the United States in the 20th Century.
  • Prostate Cancer Biology.
  • Small Business Innovation Research Program (SBIR) EDI Research and Innovation.