Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC)

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer development and progression are driven by androgen receptor (AR) activation.
• Current anti-androgen therapies targeting the AR Ligand Binding Domain (LBD) face challenges due to adverse effects and resistance mediated by AR splice variants like AR-V7.
• Chemoresistant castration-resistant prostate cancer (CRPC) presents a significant clinical challenge.

Purpose of the Study:

• To review the role of AR variants, specifically AR-V7, in CRPC.
• To investigate the therapeutic potential of natural compounds and their derivatives in targeting AR and its splice variants.
• To explore natural product-based strategies for overcoming resistance in advanced prostate cancer.

Main Methods:

• Literature review focusing on AR variants in CRPC.
• Analysis of research on natural compounds and their analogs as inhibitors of AR and AR splice variants.
• Examination of studies investigating the efficacy and limitations of natural derivatives in preclinical and clinical settings.

Main Results:

• AR splice variants, particularly AR-V7, are implicated in treatment resistance in CRPC.
• Natural compounds and their derivatives demonstrate potential for selective inhibition of AR splice variants.
• Despite bioavailability and efficacy constraints, natural derivatives show promise in treating chemoresistant prostate cancer.

Conclusions:

• Natural compounds offer a promising avenue for developing novel therapies against AR-driven prostate cancer, especially in resistant forms.
• Targeting AR splice variants with natural derivatives may provide a lower toxicity alternative to conventional treatments.
• Further research into optimizing the bioavailability and efficacy of natural compounds is crucial for clinical translation.