Inhibition of breast cancer growth with AN-329, a novel Hsp110 inhibitor, by inactivating p-STAT3/c-Myc axis

Abstract

Breast cancer, a leading cause of cancer-related mortality in women, is characterized by its propensity for metastasis. Heat shock protein 110 (Hsp110), a molecular chaperone encoded by the HSPH1 gene, has been implicated in cancer progression, including breast cancer, where it is upregulated and associated with worse outcomes. However, the role of Hsp110 in breast cancer pathogenesis and its potential as a therapeutic target have not been thoroughly investigated. This study utilized the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to analyze HSPH1 gene expression in breast cancer and its correlation with tumor progression and survival. Furthermore, a comprehensive screen of the Specs database led to the identification of AN-329, a novel inhibitor that binds directly to the nucleotide-binding domain of Hsp110, neutralizing its chaperone activity and inhibiting breast cancer cell growth. AN-329 was validated in vitro for its antitumor efficacy and was found to regulate the cell cycle through the p-STAT3/c-Myc axis. This work suggests that AN-329 could be a promising lead for developing innovative therapeutic agents against breast cancer, warranting further research and potential clinical translation.