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

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 KumarCatherine C. Going, Donna M. Peehl, Scott J. Dixon, Richard N. Zare, James D. Brooks, Sharon J. Pitteri, Sanjay V. Malhotra, Tanya Stoyanova

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number100502
JournalCell Reports Medicine
Volume3
Issue number2
DOIs
StatePublished - Feb 15 2022
Externally publishedYes

Keywords

  • HSP90
  • combination therapy
  • glycolysis
  • metabolism
  • prostate cancer
  • therapeutics
  • therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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