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Updated: May 15, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention

Shidong Jia1, Xueliang Gao, Sang Hyun Lee

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Cancer Discovery
|December 22, 2012
PubMed
Abstract

Insights

Androgen deprivation therapy may worsen prostate cancer in PTEN-deficient tumors. Targeting PI3K and MAPK pathways shows promise for treating castration-resistant prostate cancer (CRPC) in these cases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Prostate cancer chemoprevention is desirable but faces challenges.
  • 5α-reductase inhibitors have shown mixed results in clinical trials.
  • PTEN loss is a common genetic alteration in high-grade prostatic intraepithelial neoplasia (HG-PIN).

Purpose of the Study:

  • To investigate the effects of androgen deprivation on PTEN-deficient prostate cancer.
  • To explore alternative therapeutic strategies targeting signaling pathways.
  • To evaluate the efficacy of PI3K and MAPK pathway inhibition in CRPC.

Main Methods:

  • Utilized a preclinical mouse model of PTEN-loss-induced HG-PIN.
  • Administered surgical castration and MDV3100 (antiandrogen therapy).
  • Investigated genetic and pharmacologic inhibition of the PI3K pathway.
  • Assessed concurrent PI3K and MAPK pathway inhibition.

Main Results:

  • Androgen deprivation accelerated HG-PIN progression to castration-resistant prostate cancer (CRPC) in PTEN-null mice.
  • PI3K pathway inhibition reversed the HG-PIN phenotype.
  • Combined PI3K and MAPK inhibition blocked the growth of PTEN-null CRPC.

Conclusions:

  • Antiandrogen chemoprevention may have adverse effects in PTEN-deficient prostate cancer.
  • PI3K-targeted therapies are a promising alternative for patients with PTEN-deficient tumors.
  • Targeted inhibition of PI3K and MAPK pathways offers a potential treatment strategy for CRPC.

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