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Updated: May 11, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A preclinical xenograft model identifies castration-tolerant cancer-repopulating cells in localized prostate tumors
Roxanne Toivanen1, Mark Frydenberg, Declan Murphy
1Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
Abstract:
A lack of clinically relevant experimental models of human prostate cancer hampers evaluation of potential therapeutic agents. Currently, androgen deprivation therapy is the gold standard treatment for advanced prostate cancer, but inevitably, a subpopulation of cancer cells survives and repopulates the tumor. Tumor cells that survive androgen withdrawal are critical therapeutic targets for more effective treatments, but current model systems cannot determine when they arise in disease progression and are unable to recapitulate variable patient response to treatment. A model system was developed in which stromal-supported xenografts from multiple patients with early-stage localized disease can be tested for response to castration. The histopathology of these xenografts mimicked the original tumors, and short-term host castration resulted in reduced proliferation and increased apoptosis in tumor cells. After 4 weeks of castration, residual populations of quiescent, stem-like tumor cells remained. Without subsequent treatment, these residual cells displayed regenerative potential, because testosterone readministration resulted in emergence of rapidly proliferating tumors. Therefore, this model may be useful for revealing potential cellular targets in prostate cancer, which exist before the onset of aggressive incurable disease. Specific eradication of these regenerative tumor cells that survive castration could then confer survival benefits for patients.
Insights
Developing new prostate cancer models is crucial for testing therapies. This study created a model to identify and target cancer cells that survive androgen deprivation therapy, potentially improving patient outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Prostate Cancer Research
Background:
- Clinically relevant experimental models for human prostate cancer are lacking, hindering therapeutic agent evaluation.
- Androgen deprivation therapy (ADT) is standard for advanced prostate cancer, but resistant cells survive and repopulate tumors.
- Current models fail to identify when resistant cells emerge or replicate variable patient responses.
Purpose of the Study:
- To develop a stromal-supported xenograft model for testing early-stage prostate cancer response to castration.
- To investigate the behavior of residual tumor cells following androgen withdrawal.
- To identify potential cellular targets present before aggressive disease onset.
Main Methods:
- Developed patient-derived, stromal-supported xenografts from early-stage prostate cancer.
- Administered short-term host castration to assess tumor response.
- Analyzed tumor cell proliferation, apoptosis, and regenerative potential after testosterone readministration.
Main Results:
- Xenograft histopathology accurately mimicked original patient tumors.
- Castration led to reduced proliferation and increased apoptosis in xenografted tumor cells.
- Residual quiescent, stem-like tumor cells survived castration and regenerated tumors upon testosterone reintroduction.
Conclusions:
- The developed xenograft model effectively mimics human prostate cancer response to castration.
- Quiescent, stem-like cells surviving ADT represent a critical therapeutic target.
- Targeting these regenerative cells could offer survival benefits for prostate cancer patients.
