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Updated: Mar 26, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Novel non-AR therapeutic targets in castrate resistant prostate cancer
Paul J Toren1, Martin E Gleave1
1Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Castrate resistant prostate cancer (CRPC) remains a disease with significant morbidity and mortality. The recent approval of abiraterone and enzalutamide highlight the improvements which can be made targeting the androgen receptor (AR) axis. Nonetheless, resistance inevitably develops and there is continued interest in targeting alternate pathways which cause disease resistance and progression. Here, we review non-AR targets in CRPC, with an emphasis on novel agents now in development. This includes therapeutics which target the tumour microenvironment, the bone metastatic environment, microtubules, cellular energetics, angiogenesis, the stress response, survival proteins, intracellular signal transduction, DNA damage repair and dendritic cells. Understanding the hallmarks of prostate cancer resistance in CRPC has led to the identification and development of these new targets. We review the molecular rationale, as well at the clinical experience for each of these different classes of agents which are in clinical development.
Insights
Castrate-resistant prostate cancer (CRPC) research explores new non-androgen receptor (AR) targets. Novel agents targeting tumor microenvironment, energetics, and DNA repair offer promising avenues for treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Castrate-resistant prostate cancer (CRPC) presents significant morbidity and mortality.
- Current treatments targeting the androgen receptor (AR) axis, like abiraterone and enzalutamide, show efficacy but resistance develops.
- There is a critical need to identify and target alternative pathways driving CRPC progression.
Purpose of the Study:
- To review novel non-AR targets in castrate-resistant prostate cancer.
- To emphasize emerging therapeutic agents currently in development for CRPC.
- To understand the molecular rationale and clinical experience of these new agents.
Main Methods:
- Literature review of non-AR targets in CRPC.
- Analysis of novel agents targeting various pathways including tumor microenvironment, bone metastasis, cellular energetics, angiogenesis, and DNA damage repair.
- Examination of molecular rationale and clinical development status.
Main Results:
- Several non-AR pathways are implicated in CRPC resistance.
- Novel therapeutic strategies are under investigation targeting tumor microenvironment, cellular energetics, DNA damage repair, and immune cells.
- These agents represent a diverse range of approaches to overcome treatment resistance.
Conclusions:
- Understanding CRPC resistance mechanisms is key to identifying new therapeutic targets.
- Emerging non-AR targeting agents show potential to improve outcomes in advanced prostate cancer.
- Continued research and clinical trials are essential to evaluate the efficacy of these novel therapies.
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