The novel Hsp90 inhibitor NXD30001 induces tumor regression in a genetically engineered mouse model of glioblastoma multiforme.

Molecular Cancer Therapeutics
Haihao ZhuAl Charest

Abstract

Glioblastoma multiforme (GBM) has an abysmal prognosis. We now know that the epidermal growth factor receptor (EGFR) signaling pathway and the loss of function of the tumor suppressor genes p16Ink4a/p19ARF and PTEN play a crucial role in GBM pathogenesis: initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. We have recently shown that this genetic combination is sufficient to promote the development of GBM in adult mice. Therapeutic agents raised against single targets of the EGFR signaling pathway have proven rather inefficient in GBM therapy, showing the need for combinatorial therapeutic approaches. An effective strategy for concurrent disruption of multiple signaling pathways is via the inhibition of the molecular chaperone heat shock protein 90 (Hsp90). Hsp90 inhibition leads to the degradation of so-called client proteins, many of which are key effectors of GBM pathogenesis. NXD30001 is a novel second generation Hsp90 inhibitor that shows improved pharmacokinetic parameters. Here we show that NXD30001 is a potent inhibitor of GBM cell growth in vitro consistent with its capacity to inhibit several key targets and regulators of GBM biology. ...Continue Reading

References

Sep 25, 2004·Journal of Cellular Physiology·Motohiro NomuraDavid Zagzag
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 11, 2005·The New England Journal of Medicine·Monika E HegiRoger Stupp
Apr 28, 2005·Current Topics in Medicinal Chemistry·Hiroshi HiraiYoshikazu Iwasawa
May 4, 2005·Current Neurology and Neuroscience Reports·Roger StuppMonika E Hegi
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jann N SarkariaC David James
Oct 24, 2006·Cell·William Y Kim, Norman E Sharpless
Jun 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Leslie L MuldoonEdward A Neuwelt
Apr 23, 2008·Current Protocols in Neuroscience·D E Weinstein
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Haihao ZhuAl Charest
May 5, 2009·Bioorganic & Medicinal Chemistry Letters·Cuihua WangNicolas Winssinger
Jul 16, 2009·Genesis : the Journal of Genetics and Development·Steve WoolfendenAl Charest
Jul 25, 2009·Nature Reviews. Cancer·Jeffrey A Engelman
Oct 27, 2009·Chembiochem : a European Journal of Chemical Biology·Sofia BarluengaNicolas Winssinger
Oct 29, 2009·Current Topics in Medicinal Chemistry·Robert L Matts, Jacob R Manjarrez
Oct 29, 2009·Current Topics in Medicinal Chemistry·Y S KimJ B Trepel

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Citations

Feb 1, 2012·The Cancer Journal·Jiangbing ZhouW Mark Saltzman
Jul 11, 2014·Cellular and Molecular Life Sciences : CMLS·Iva Simeonova, Emmanuelle Huillard
Jun 21, 2011·Brain Research Bulletin·Ralf S SchmidC Ryan Miller
Dec 6, 2011·American Journal of Medical Genetics. Part a·Jaishri O BlakeleyMarco Giovannini
Aug 16, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Daniel A SmithSanford I Bernstein
Mar 10, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sara Melo-LimaFaustino Mollinedo
Sep 24, 2014·Neuro-oncology·Robert S McNeillC Ryan Miller
Apr 6, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shinji YamazakiPaolo Vicini
Feb 5, 2016·Journal of Neuro-oncology·Randy van OmmerenMatthew O Hebb
May 30, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karo TanakaMarco Giovannini
Sep 2, 2021·Neuro-oncology Advances·Alexander F HaddadNicholas A Butowski

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