A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Persistent androgen receptor (AR) signaling drives prostate cancer (PCa).
• Treatment resistance to AR pathway inhibitors like Enzalutamide is often associated with the emergence of truncated AR isoforms known as AR variants (AR-Vs).
• AR-Vs lack the ligand-binding domain, contributing to a more aggressive PCa phenotype.

Purpose of the Study:

• To review the mechanisms by which AR-Vs promote aggressive PCa.
• To discuss the role of AR-V7, the most common variant, and its regulated genes in PCa progression.
• To explore the potential of AR-Vs and their downstream targets as therapeutic targets for advanced prostate cancer.

Main Methods:

• Literature review of studies on AR signaling, AR variants, and prostate cancer.
• Analysis of experimentally validated AR-V7 regulated genes.
• Discussion of oncogenic pathways regulated by AR-Vs.
• Evaluation of potential drug targets for AR-V driven PCa.

Main Results:

• AR-Vs significantly contribute to the progression of prostate cancer.
• AR-V7 regulates specific target genes involved in oncogenic pathways, promoting aggressive disease.
• Downstream protein products of AR-V7 are potential therapeutic targets.

Conclusions:

• Targeting both full-length AR and AR-Vs is crucial for effective prostate cancer treatment.
• Understanding AR-V-regulated genes is essential for developing new AR inhibitors and evaluating treatment efficacy.
• AR-V7 and its downstream targets represent promising avenues for novel PCa therapies.