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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Androgen annihilation as a new therapeutic paradigm in advanced prostate cancer
Kyle O Rove1, E David Crawford
1University of Colorado, Anschutz Medical Campus, Division of Urology, Aurora, CO 80045, USA.
Purpose Of Review:
Treatment of all stages of prostate cancer has changed considerably in recent years, as our understanding of its biochemical pathways has improved. Testosterone, true to Huggin's original observation, remains a key player not only in newly diagnosed prostate cancer but also in castration-resistant prostate cancer, and our understanding of how to combine and sequence drugs that attack these pathways continues to grow. New US Food and Drugs Administration approved pharmaceutical agents further eliminate testosterone ligand or its activity via inhibition of key synthetic enzymes and through strong inhibition of the androgen receptor.
Recent Findings:
This review will briefly examine our knowledge of the complex relationship between testosterone, androgen receptor and advanced prostate cancer, discuss the limits of traditional androgen deprivation therapy in the form of gonadotropin-releasing hormone agonists and newer antagonists, examine combination therapies, including combined androgen blockade and newer studies with 5α-reductase inhibitors, and overview two new therapeutics that target hormonal pathways.
Summary:
This review provides guidance on trials that examine combination therapies in various prostate cancer disease states. Androgens and prostate cancer remain inexorably linked, and this review will shed light on renewed focus on eliminating activity of this trophic ligand.
Insights
Testosterone remains central to prostate cancer treatment, even in advanced and castration-resistant forms. New therapies and combination treatments targeting testosterone pathways offer improved strategies for managing prostate cancer.
Area of Science:
- Oncology
- Endocrinology
- Biochemistry
Background:
- Prostate cancer treatment has evolved with a deeper understanding of its biochemical pathways.
- Testosterone plays a critical role in both newly diagnosed and castration-resistant prostate cancer.
- New pharmaceutical agents target testosterone pathways by inhibiting synthesis or androgen receptor activity.
Purpose of the Study:
- To review the relationship between testosterone, androgen receptor, and advanced prostate cancer.
- To discuss the limitations of traditional androgen deprivation therapy (ADT).
- To examine emerging combination therapies and new therapeutics targeting hormonal pathways.
Main Methods:
- Literature review of recent advancements in prostate cancer treatment.
- Analysis of current understanding of testosterone's role in prostate cancer.
- Overview of novel pharmaceutical agents and combination strategies.
Main Results:
- Traditional ADT (GnRH agonists/antagonists) has limitations.
- Combination therapies, including combined androgen blockade and 5α-reductase inhibitors, show promise.
- New therapeutics offer novel approaches to inhibit testosterone ligand activity.
Conclusions:
- Androgens are fundamentally linked to prostate cancer progression.
- Combination therapies are crucial for managing various prostate cancer states.
- Renewed focus on eliminating androgen activity is key for effective treatment.
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