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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
Drug Resistance and Cardiovascular Safety of Second-Generation Anti-Androgens in Patients with Advanced Prostate
Venus Shahabi Raberi1, Akram Shariati1, Mohsen Abbasnezhad2
1Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Abstract:
Prostate cancer is recognized as one of the most common cancers affecting the male population. The prostate is revealed to be a hormone-dependent tissue as testosterone and dihydrotestosterone could bind to the androgen receptor, activate it, and initiate the nuclear translocation of this receptor, followed by subsequent signaling cascades. Regarding this androgen dependency on the prostate, it is believed that androgen deprivation therapies can confront aggressive prostate cancer as a first-line treatment. However, prostate cancer could overcome hormone deprivation strategies through several cellular mechanisms, such as intratumoral androgen production and the production of ligand-independent androgen receptor splice variants, known clinically as castration-resistant prostate cancer. Due to the limited efficacy of first-generation anti-androgens in complete blockage of androgen receptor activity, recently, four second-generation anti-androgens, including abiraterone acetate, enzalutamide, apalutamide, and darolutamide approved by the United States Food and Drug Administration, and considered standard of care for patients with advanced prostate cancer. In addition to some reports of drug resistance treatments, cardiotoxicity, including heart failure, ventricular repolarization, hypertension, myocarditis, atrial fibrillation, and ischemic heart diseases, is commonly observed in patients who underwent abiraterone acetate and/or enzalutamide therapy. However, cardiotoxicity has rarely been observed after treatments of apalutamide and/or darolutamide.
Insights
Second-generation anti-androgens like abiraterone and enzalutamide treat advanced prostate cancer but can cause cardiotoxicity. Apalutamide and darolutamide offer similar efficacy with a lower risk of heart problems.
Area of Science:
- Oncology
- Pharmacology
- Cardiology
Background:
- Prostate cancer is a common malignancy dependent on androgens.
- Androgen deprivation therapy is a primary treatment, but resistance leads to castration-resistant prostate cancer.
- Second-generation anti-androgens (abiraterone, enzalutamide, apalutamide, darolutamide) are standard care for advanced prostate cancer.
Purpose of the Study:
- To review the efficacy and cardiotoxicity profiles of second-generation anti-androgens in advanced prostate cancer.
- To compare the cardiotoxicity risks associated with different anti-androgen therapies.
Main Methods:
- Literature review of clinical trials and studies on second-generation anti-androgens.
- Analysis of reported efficacy and adverse events, with a focus on cardiotoxicity.
- Comparison of cardiotoxicity incidence between abiraterone/enzalutamide and apalutamide/darolutamide.
Main Results:
- Abiraterone acetate and enzalutamide are effective but commonly associated with cardiotoxicity (heart failure, arrhythmias, hypertension).
- Apalutamide and darolutamide demonstrate comparable efficacy in treating advanced prostate cancer.
- Cardiotoxicity is rarely reported with apalutamide and darolutamide treatments.
Conclusions:
- Second-generation anti-androgens represent significant advancements in prostate cancer treatment.
- While abiraterone and enzalutamide carry notable cardiotoxicity risks, apalutamide and darolutamide appear safer from a cardiovascular standpoint.
- Further research should focus on optimizing anti-androgen therapy to maximize efficacy while minimizing adverse cardiovascular events.
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