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Updated: Jul 9, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Mechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities

Eun-Mi Yu1, Min Woo Hwang2, Jeanny B Aragon-Ching1

  • 1GU Medical Oncology, Inova Schar Cancer Institute, Fairfax, VA, USA.

Research and Reports in Urology
|December 5, 2023
PubMed

Insights

Prostate cancer progresses to castration-resistant disease despite androgen deprivation therapy. This review explores resistance mechanisms and targeted therapies for metastatic castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Cancer Biology

Background:

  • Prostate cancer is a leading non-cutaneous cancer in American men.
  • Androgen deprivation therapy is a primary treatment, but resistance leading to castration-resistant prostate cancer is common.
  • Tumorigenesis and metastasis involve complex molecular mechanisms.

Purpose of the Study:

  • To review the mechanisms driving progression in prostate cancer.
  • To highlight therapeutic targets in metastatic castration-resistant prostate cancer.
  • To discuss key clinical trials evaluating drugs targeting these pathways.

Main Methods:

  • Literature review of scientific articles and clinical trials.
  • Focus on molecular pathways implicated in prostate cancer progression and resistance.
  • Analysis of therapeutic strategies for metastatic castration-resistant prostate cancer.

Main Results:

  • Aberrant PI3K/AKT signaling due to PTEN loss is a key mechanism.
  • Epithelial-mesenchymal transition pathways contribute to metastasis.
  • Homologous recombination repair and DNA repair pathways are involved in resistance.

Conclusions:

  • Understanding resistance mechanisms is crucial for effective prostate cancer treatment.
  • Targeting specific pathways offers therapeutic opportunities in metastatic castration-resistant prostate cancer.
  • Ongoing clinical trials are evaluating novel drug combinations for advanced disease.
Keywords:
androgen receptor pathway inhibitorscastration-resistant prostate cancerepithelial mesenchymal transitionmetastasispoly-ADP ribose pathway inhibitorsprostate cancer

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