Table 2.

Novel AR targeted therapies.

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 [147–149].