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Updated: Apr 6, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Androgen deprivation of prostate cancer: Leading to a therapeutic dead end
Arndt Katzenwadel1, Philipp Wolf2
1Department of Urology, Medical Center, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
Abstract:
Androgen deprivation therapy (ADT) is considered as the standard therapy for men with de novo or recurrent metastatic prostate cancer. ADT commonly leads to initial biochemical and clinical responses. However, several months after the beginning of treatment, tumors become castration-resistant and virtually all patients show disease progression. At this stage, tumors are no longer curable and cancer treatment options are only palliative. In this review, we describe molecular alterations in tumor cells during ADT, which lead to deregulation of different signaling pathways and castration-resistance, and how they might interfere with the clinical outcome of different second-line therapeutics. A recent breakthrough finding that early chemotherapy is associated with a significant survival benefit in metastatic hormone-sensitive disease highlights the fact that there is time for a fundamental paradigm shift in the treatment of advanced prostate cancer. Therapeutic intervention seems to be indicated before a castration-resistant stage is reached to improve therapeutic outcome and to reduce undesirable side effects.
Insights
Androgen deprivation therapy (ADT) for metastatic prostate cancer often leads to resistance. Early chemotherapy shows survival benefits, suggesting a paradigm shift towards earlier intervention before castration resistance develops.
Area of Science:
- Oncology
- Cancer Biology
Background:
- Androgen deprivation therapy (ADT) is standard for metastatic prostate cancer.
- ADT initially responds but tumors frequently develop castration resistance, limiting treatment options.
Purpose of the Study:
- To review molecular alterations driving castration resistance during ADT.
- To explore how these alterations impact second-line therapies.
- To discuss a paradigm shift towards earlier treatment interventions.
Main Methods:
- Review of molecular mechanisms of castration resistance.
- Analysis of signaling pathways affected by ADT.
- Evaluation of recent findings on early chemotherapy in metastatic hormone-sensitive prostate cancer.
Main Results:
- ADT induces molecular changes leading to castration resistance and signaling pathway deregulation.
- These alterations can affect the efficacy of subsequent treatments.
- Early chemotherapy in hormone-sensitive disease offers significant survival advantages.
Conclusions:
- Understanding molecular alterations is key to overcoming ADT resistance.
- A paradigm shift towards earlier therapeutic intervention before castration resistance is warranted.
- Earlier treatment may improve outcomes and reduce side effects in advanced prostate cancer.
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