SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer

• DOI: 10.1016/j.xcrm.2021.100502
• Publication Date: 2022-02-02T16:31:23Z
• Authors: Meghan A. Rice; Vineet Kumar; Dhanir Tailor; Fernando Jose Gar...; En-Chi Hsu; Shiqin Liu; Abel Bermudez; Vijayalakshmi Kan...; Vishnu Shankar; Zintis Inde; Busola Ruth Alabi; Arvind Muruganantham; Michelle Shen; Mallesh Pandrala; Rosalie Nolley; Merve Aslan; Ali Ghoochani; Arushi Agarwal; Mark Buckup; Manoj Kumar; Catherine C. Going; Donna M. Peehl; Scott J. Dixon; Richard N. Zare; James D. Brooks; Sharon J. Pitteri; Sanjay V. Malhotra; Tanya Stoyanova
• Keywords: Ex vivo; Hsp90 inhibitor

Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe small molecule, SU086, as therapeutic strategy for cancer. demonstrate that SU086 inhibits growth cells in vitro, cell-line and patient-derived xenografts vivo, ex vivo patient specimens. Furthermore, combination standard care second-generation anti-androgen therapies displays increased impairment cell tumor vitro vivo. Cellular thermal shift assay reveals binds to heat shock protein 90 (HSP90) leads decrease HSP90 levels. Proteomic profiling demonstrates decreases HSP90. Metabolomic perturbation glycolysis. Our study identifies treatment single agent or when combined anti-androgens.