Targeting JWA for Cancer Therapy: Functions, Mechanisms and Drug Discovery

SIMPLE SUMMARY: JWA has been identified as a potential therapeutic target for several cancers. In this review, we summarize the tumor suppressive functions of the JWA gene and its role in anti-cancer drug development. The focus is on elucidating the key regulatory proteins up and downstream of JWA and their signaling networks. We also discuss current strategies for targeting JWA (JWA peptides, small molecule agonists, and JWA-targeted Pt (IV) prodrugs). ABSTRACT: Tumor heterogeneity limits the precision treatment of targeted drugs. It is important to find new tumor targets. JWA, also known as ADP ribosylation factor-like GTPase 6 interacting protein 5 (ARL6IP5, GenBank: AF070523, 1998), is a microtubule-associated protein and an environmental response gene. Substantial evidence shows that JWA is low expressed in a variety of malignancies and is correlated with overall survival. As a tumor suppressor, JWA inhibits tumor progression by suppressing multiple oncogenes or activating tumor suppressor genes. Low levels of JWA expression in tumors have been reported to be associated with multiple aspects of cancer progression, including angiogenesis, proliferation, apoptosis, metastasis, and chemotherapy resistance. In this review, we will discuss the structure and biological functions of JWA in tumors, examine the potential therapeutic strategies for targeting JWA and explore the directions for future investigation.