Table 2 Novel AR targeted therapies.
From: Second generation androgen receptor antagonists and challenges in prostate cancer treatment
Agents/technologies | Mechanisms and preclinical/clinical evidence |
|---|---|
AR DBD inhibitors | AR binding to the DNA via its DBD is an essential step in the regulation of gene transcription by both full-length and variant forms of AR [163]. AR DBD inhibitors can effectively inhibit the activity of truncated ARVs and repress PCa growth in vitro and in vivo [129, 134, 164]. |
AR NTD inhibitors | The AR NTD is essential for AR transactivation, and NTD deletion renders AR transcriptionally inactive [165]. A phase I trial has established the safety of EPI-506 and provides proof of concept for targeting the AR NTD [133]. |
AR-targeted PROTACs | PROTACs technology has emerged as a promising approach for targeted therapy in various diseases, particularly in cancer [136]. ARV-110 targets AR and is safe and has efficacy in mCRPC patients [137, 138]. A phase I/II dose escalation study is currently recruiting mCRPC patients to assess the tolerability and safety of ARV-110 (NCT03888612). |
AR-targeted CRISPR-Cas13 | CRISPR/Cas13 targeting of oncogenes has been proven to repress the growth of multiple types of cancer in vitro and in vivo [147,148,149]. |
