@article{416f0421012c4fb5959e80ef44111c3f,
title = "SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer",
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.",
keywords = "HSP90, combination therapy, glycolysis, metabolism, prostate cancer, therapeutics, therapy",
author = "Rice, {Meghan A.} and Vineet Kumar and Dhanir Tailor and Garcia-Marques, {Fernando Jose} and Hsu, {En Chi} and Shiqin Liu and Abel Bermudez and Vijayalakshmi Kanchustambham and Vishnu Shankar and Zintis Inde and Alabi, {Busola Ruth} and Arvind Muruganantham and Michelle Shen and Mallesh Pandrala and Rosalie Nolley and Merve Aslan and Ali Ghoochani and Arushi Agarwal and Mark Buckup and Manoj Kumar and Going, {Catherine C.} and Peehl, {Donna M.} and Dixon, {Scott J.} and Zare, {Richard N.} and Brooks, {James D.} and Pitteri, {Sharon J.} and Malhotra, {Sanjay V.} and Tanya Stoyanova",
note = "Funding Information: We would like to thank members of the Stoyanova, Malhotra, Brooks, Peehl, Dixon, Pitteri, and Zare laboratories. T.S. is supported by the Canary Foundation and the National Institute of Health/National Cancer Institute (NCI) R37CA240822 and R01CA244281 . M.A.R. is supported by the U.S. Department of Defence Congressionally Directed Medical Research Programs Award No. W81XWH1810141 . S.V.M. is supported by National Institutes of Health (NIH) R01 DK114174 and the Stanford Cancer Institute . R.N.Z., V. Kanchustambham, and J.D.B. are supported by NIH CA229933 . J.D.B. is supported by NIH CA196387 . S.J.D. is supported by 1R01GM122923 from the NIH and a Damon Runyon-Rachleff Innovation award . Opinions, interpretation, conclusions, and recommendations are those of the authors and not necessarily endorsed by the funding agencies. Funding Information: We would like to thank members of the Stoyanova, Malhotra, Brooks, Peehl, Dixon, Pitteri, and Zare laboratories. T.S. is supported by the Canary Foundation and the National Institute of Health/National Cancer Institute (NCI) R37CA240822 and R01CA244281. M.A.R. is supported by the U.S.Department of Defence Congressionally Directed Medical Research Programs Award No. W81XWH1810141. S.V.M. is supported by National Institutes of Health (NIH) R01 DK114174 and the Stanford Cancer Institute. R.N.Z. V. Kanchustambham, and J.D.B. are supported by NIH CA229933. J.D.B. is supported by NIH CA196387. S.J.D. is supported by 1R01GM122923 from the NIH and a Damon Runyon-Rachleff Innovation award. Opinions, interpretation, conclusions, and recommendations are those of the authors and not necessarily endorsed by the funding agencies. M.A.R. V. Kumar, D.T. S.V.M. and T.S. designed research. M.A.R. V. Kumar, D.T. F.J.G.-M. A.B. V. Kanchustambham, V.S. Z.R.I. R.N. A.G. S.L. M.A. A.A. M.B. E.-C.H. B.R.A. M.K. A.M. M.S. and C.C.G. performed research. M.A.R. V. Kumar, V. Kanchustambham, D.T. M.P. E.C. D.M.P. S.J.D. R.N.Z. J.D.B. S.V.M. and T.S. contributed reagents/tools. M.A.R. D.T. F.J.G.-M. V. Kanchustambham, V.S. S.P. S.V.M. and T.S. analyzed data. M.A.R. V. Kumar, D.T. A.B. V. Kanchustambham, V.S. S.J.D. D.M.P. J.D.B. S.V.M. and T.S. wrote the manuscript. T.S. S.V.M. M.A.R. V. Kumar, and D.T. are contributors to a provisional patent application, U.S. Application Serial No. 63/023,031, ?Methoxychalcone Derivative and Uses Thereof.? T.S. currently has consulting relationships with Dren Bio. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2022",
month = feb,
day = "15",
doi = "10.1016/j.xcrm.2021.100502",
language = "English (US)",
volume = "3",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "2",
}