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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 androgen receptor signalling axis in castration-resistant prostate cancer (CRPC)
Che-Kai Tsao1, Matthew D Galsky, Alexander C Small
1Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
What's known on the subject? and What does the study add? Castration resistance has been appreciated for decades, and several mechanisms theorising on this effect have been proposed. A rich pipeline of novel agents, including abiraterone and MDV3100, have provided proof of principle that novel agents targeting the AR signalling pathway with superior selectivity and activity than predecessors have yielded significant clinical benefit for patients with metastatic castration-resistant prostate cancer. Our review provides an update in the development of several novel agents targeting the AR signalling pathway now in clinical testing, as well as review novel therapies in development with distinct mechanisms of action showing promising preclinical activity. • Despite undergoing local therapy with curative intent, 20-30% of patients with prostate cancer will ultimately development metastatic disease, leading to morbidity and mortality. • Androgen-deprivation therapy (ADT) for men with metastatic prostate cancer results in transient clinical benefit, but ultimately, cancers progress despite castrate levels of serum testosterone, a clinical state classically referred to as 'hormone refractory' disease. • In this review, we examine mechanisms of resistance to ADT that have redefined our understanding of the more appropriately termed 'castration resistant' disease, and have paved the way for a new generation of therapeutics targeting the androgen signalling axis in advanced prostate cancer.
Insights
New therapies targeting the androgen receptor (AR) signaling pathway offer significant clinical benefit for metastatic castration-resistant prostate cancer. This review updates on novel agents in clinical testing and promising preclinical therapies.
Area of Science:
- Urology and Oncology
- Molecular Biology and Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) affects 20-30% of patients despite curative-intent local therapy.
- Androgen-deprivation therapy (ADT) provides only transient benefit in mCRPC, with cancer progressing despite low testosterone levels.
- Understanding resistance mechanisms has redefined 'hormone refractory' disease as 'castration-resistant' disease.
Purpose of the Study:
- To review novel agents targeting the androgen receptor (AR) signaling pathway for advanced prostate cancer.
- To provide an update on agents currently in clinical trials.
- To examine novel therapies with distinct mechanisms showing preclinical promise.
Main Methods:
- Literature review of current clinical trials and preclinical studies.
- Analysis of novel therapeutic agents targeting the AR signaling pathway.
- Examination of distinct mechanisms of action for emerging prostate cancer therapies.
Main Results:
- Novel agents targeting the AR signaling pathway, such as abiraterone and MDV3100, demonstrate significant clinical benefit in mCRPC.
- A pipeline of new agents targeting the AR pathway is in clinical testing.
- Novel therapies with distinct mechanisms show promising preclinical activity.
Conclusions:
- Targeting the AR signaling axis with novel agents represents a new generation of therapeutics for advanced prostate cancer.
- Continued research into resistance mechanisms and novel therapeutic strategies is crucial for improving outcomes in mCRPC.
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