SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer
Year: 2022
Type: article
Abstract: Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe a small molecule, SU086, as a therapeutic strategy for advanced prostate cancer. We demonstrate that SU086 inhibits the growth of prostate cancer cells in vitro , cell-line and patient-derived xenografts in vivo , and ex vivo prostate cancer patient specimens. Furthermore, SU086 in combination with standard of care second-generation anti-androgen therapies displays increased impairment of prostate cancer cell and tumor growth in vitro and in vivo . Cellular thermal shift assay reveals that SU086 binds to heat shock protein 90 (HSP90) and leads to a decrease in HSP90 levels. Proteomic profiling demonstrates that SU086 binds to and decreases HSP90. Metabolomic profiling reveals that SU086 leads to perturbation of glycolysis. Our study identifies SU086 as a treatment for advanced prostate cancer as a single agent or when combined with second-generation anti-androgens.
Source: Cell Reports Medicine
Authors: Meghan A. Rice, Vineet Kumar, Dhanir Tailor, Fernando Jose Garcia-Marques, En-Chi Hsu, Shiqin Liu, Abel Bermudez, Vijayalakshmi Kanchustambham, 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
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Damon Runyon Cancer Research Foundation, Canary Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Stanford Cancer Institute, Congressionally Directed Medical Research Programs
OpenAlex ID: W4210657293