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Updated: Apr 14, 2026
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Targeting the adaptive molecular landscape of castration-resistant prostate cancer
Alexander W Wyatt1, Martin E Gleave1
1Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada awyatt@prostatecentre.com m.gleave@ubc.ca.
Abstract:
Castration and androgen receptor (AR) pathway inhibitors induce profound and sustained responses in advanced prostate cancer. However, the inevitable recurrence is associated with reactivation of the AR and progression to a more aggressive phenotype termed castration-resistant prostate cancer (CRPC). AR reactivation can occur directly through genomic modification of the AR gene, or indirectly via co-factor and co-chaperone deregulation. This mechanistic heterogeneity is further complicated by the stress-driven induction of a myriad of overlapping cellular survival pathways. In this review, we describe the heterogeneous and evolvable molecular landscape of CRPC and explore recent successes and failures of therapeutic strategies designed to target AR reactivation and adaptive survival pathways. We also discuss exciting areas of burgeoning anti-tumour research, and their potential to improve the survival and management of patients with CRPC.
Insights
Advanced prostate cancer often recurs as castration-resistant prostate cancer (CRPC) due to androgen receptor (AR) reactivation. Understanding CRPC
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Advanced prostate cancer initially responds to castration and androgen receptor (AR) pathway inhibitors.
- Recurrence leads to castration-resistant prostate cancer (CRPC), characterized by AR reactivation.
- AR reactivation mechanisms include direct genomic changes and indirect co-factor/co-chaperone deregulation.
Purpose of the Study:
- To review the heterogeneous and evolving molecular landscape of CRPC.
- To explore therapeutic strategies targeting AR reactivation and adaptive survival pathways.
- To discuss emerging anti-tumour research for improved CRPC patient outcomes.
Main Methods:
- Review of current literature on CRPC molecular mechanisms.
- Analysis of therapeutic successes and failures in targeting AR reactivation.
- Discussion of novel anti-cancer research avenues.
Main Results:
- CRPC exhibits mechanistic heterogeneity in AR reactivation.
- Cellular survival pathways are induced by stress, complicating treatment.
- Therapeutic strategies face challenges due to this complexity.
Conclusions:
- CRPC is a complex, evolving disease driven by AR reactivation.
- Targeting AR reactivation and survival pathways requires nuanced strategies.
- Emerging research holds promise for advancing CRPC treatment and patient survival.
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