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Updated: Mar 28, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: A review
Archana Anantharaman1, Terence W Friedlander1
1Genitourinary Medical Oncology Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Abstract:
Despite recent advances in the treatment of advanced prostate cancer (PCa), metastatic castrate-resistant PCa remains incurable at this time. The androgen receptor (AR) plays a key role in the development and progression of PCa, continuing to be active in most patients even after the development of castration resistance. Here, we aim to more closely review the mechanisms by which AR signaling is maintained, including AR overexpression/overamplification, intracrine androgen synthesis, AR mutations, and the development of AR splice variants. We also review therapies targeting each of these mechanisms. We also discuss the potential role of AR-CAG repeats and AR splice variants as potential biomarkers of response to hormonal manipulation therapies.
Insights
Metastatic castrate-resistant prostate cancer (PCa) is incurable. This review examines how androgen receptor (AR) signaling persists, including AR amplification, mutations, and splice variants, and discusses targeted therapies and biomarkers.
Area of Science:
- Oncology
- Urology
- Molecular Biology
Background:
- Advanced prostate cancer (PCa), particularly metastatic castrate-resistant PCa (mCRPC), presents significant therapeutic challenges.
- The androgen receptor (AR) pathway remains a critical driver of PCa progression, even in castration-resistant states.
- Understanding AR signaling maintenance is crucial for developing effective mCRPC treatments.
Purpose of the Study:
- To review the key mechanisms sustaining androgen receptor (AR) signaling in prostate cancer.
- To discuss current and emerging therapies targeting these AR-dependent mechanisms.
- To explore the potential of AR-CAG repeats and AR splice variants as predictive biomarkers.
Main Methods:
- Literature review of studies on AR signaling in prostate cancer.
- Analysis of mechanisms including AR gene amplification, intracrine androgen synthesis, AR mutations, and AR splice variants.
- Examination of therapeutic strategies targeting AR signaling pathways.
Main Results:
- AR signaling is maintained through various mechanisms: AR overexpression/overamplification, intracrine androgen synthesis, AR mutations, and AR splice variants.
- Targeted therapies are being developed to counteract these resistance mechanisms.
- AR-CAG repeat length and AR splice variants show potential as biomarkers for treatment response.
Conclusions:
- Persistent AR signaling is central to mCRPC progression.
- Targeting AR pathway vulnerabilities offers a promising therapeutic avenue.
- Biomarkers like AR-CAG repeats and splice variants may guide treatment selection for enhanced efficacy.
