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SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer.
Rice, Meghan A; Kumar, Vineet; Tailor, Dhanir; Garcia-Marques, Fernando Jose; Hsu, En-Chi; Liu, Shiqin; Bermudez, Abel; Kanchustambham, Vijayalakshmi; Shankar, Vishnu; Inde, Zintis; Alabi, Busola Ruth; Muruganantham, Arvind; Shen, Michelle; Pandrala, Mallesh; Nolley, Rosalie; Aslan, Merve; Ghoochani, Ali; Agarwal, Arushi; Buckup, Mark; Kumar, Manoj; Going, Catherine C; Peehl, Donna M; Dixon, Scott J; Zare, Richard N; Brooks, James D; Pitteri, Sharon J; Malhotra, Sanjay V; Stoyanova, Tanya.
Afiliação
  • Rice MA; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Kumar V; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Tailor D; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
  • Garcia-Marques FJ; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
  • Hsu EC; Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Liu S; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Bermudez A; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Kanchustambham V; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Shankar V; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Inde Z; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Alabi BR; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Muruganantham A; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Shen M; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Pandrala M; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Nolley R; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
  • Aslan M; Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
  • Ghoochani A; Department of Biology, Stanford University, Stanford, CA 94305, USA.
  • Agarwal A; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Buckup M; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Kumar M; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Going CC; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Peehl DM; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
  • Dixon SJ; Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA 94305, USA.
  • Zare RN; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
  • Brooks JD; Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Pitteri SJ; Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Malhotra SV; Department of Urology, Stanford University, Stanford, CA 94305, USA.
  • Stoyanova T; Department of Radiology, Stanford University, Stanford, CA 94305, USA.
Cell Rep Med ; 3(2): 100502, 2022 02 15.
Article em En | MEDLINE | ID: mdl-35243415
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Problema de saúde: 6_prostate_cancer Assunto principal: Neoplasias da Próstata / Proteômica Limite: Humans / Male Idioma: En Revista: Cell Rep Med Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Problema de saúde: 6_prostate_cancer Assunto principal: Neoplasias da Próstata / Proteômica Limite: Humans / Male Idioma: En Revista: Cell Rep Med Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos