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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Inhibition of Heat Shock Protein 90 as a Novel Platform for the Treatment of Cancer

Author(s): Chang Gao, Ya-Nan Peng, Hai-Zhou Wang, Shi-Lin Fang, Meng Zhang, Qiu Zhao and Jing Liu*

Volume 25, Issue 8, 2019

Page: [849 - 855] Pages: 7

DOI: 10.2174/1381612825666190503145944

Price: $65

Abstract

Heat shock protein 90 (Hsp90) plays an essential role in various physiological and pathological processes. It activates client proteins to participate in tumor progression. Blocking Hsp90 could enable effective antitumor effects in many tumor types, such as multiple myeloma and colon cancer. Recently, it has motivated an interest in Hsp90 inhibitors that bind to the N-terminal or C-terminal ATP pocket as antitumor drugs. We reviewed the data from experimental and clinical trials on Hsp90 inhibitors in the treatment of different malignancies to explore and summarize their antitumor mechanisms.

Keywords: Heat shock protein 90, signaling pathway, client protein, ATPase, inhibitor, cancer treatment.

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[1]
Sauvage F, Messaoudi S, Fattal E, Barratt G, Vergnaud-Gauduchon J. Heat shock proteins and cancer: How can nanomedicine be harnessed? J Control Release 2017; 248: 133-43.
[2]
Zilaee M, Shirali S. Heat Shock Proteins and Diabetes. Can J Diabetes 2016; 40(6): 594-602.
[3]
Calderwood SK. Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands? Philos Trans R Soc Lond B Biol Sci 2018; 373(1738): 373.
[4]
Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S. Heat Shock Proteins and Cancer. Trends Pharmacol Sci 2017; 38(3): 226-56.
[5]
Cardillo MR, Ippoliti F. IL-6, IL-10 and HSP-90 expression in tissue microarrays from human prostate cancer assessed by computer-assisted image analysis. Anticancer Res 2006; 26(5A): 3409-16.
[6]
Blagg BS, Kerr TD. Hsp90 inhibitors: small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation. Med Res Rev 2006; 26(3): 310-38.
[7]
Johnson JL. Evolution and function of diverse Hsp90 homologs and cochaperone proteins. Biochim Biophys Acta 2012; 1823(3): 607-13.
[8]
Nathan DF, Vos MH, Lindquist S. In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. Proc Natl Acad Sci USA 1997; 94(24): 12949-56.
[9]
Picard D, Khursheed B, Garabedian MJ, Fortin MG, Lindquist S, Yamamoto KR. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 1990; 348(6297): 166-8.
[10]
Yamaki H, Nakajima M, Shimotohno KW, Tanaka N. Molecular basis for the actions of Hsp90 inhibitors and cancer therapy. J Antibiot (Tokyo) 2011; 64(9): 635-44.
[11]
Stravopodis DJ, Margaritis LH, Voutsinas GE. Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex. Curr Med Chem 2007; 14(29): 3122-38.
[12]
Chiosis G, Caldas Lopes E, Solit D. Heat shock protein-90 inhibitors: a chronicle from geldanamycin to today’s agents. Curr Opin Investig Drugs 2006; 7(6): 534-41.
[13]
Taipale M, Jarosz DF, Lindquist S. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol 2010; 11(7): 515-28.
[14]
Pearl LH, Prodromou C. Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu Rev Biochem 2006; 75: 271-94.
[15]
Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 1997; 90(1): 65-75.
[16]
Tsutsumi S, Mollapour M, Prodromou C, et al. Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. Proc Natl Acad Sci USA 2012; 109(8): 2937-42.
[17]
Buchner J. Hsp90 & Co. - a holding for folding. Trends Biochem Sci 1999; 24(4): 136-41.
[18]
Ali MM, Roe SM, Vaughan CK, et al. Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 2006; 440(7087): 1013-7.
[19]
Hagn F, Lagleder S, Retzlaff M, et al. Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53. Nat Struct Mol Biol 2011; 18(10): 1086-93.
[20]
Prodromou C, Panaretou B, Chohan S, et al. The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of the N-terminal domains. EMBO J 2000; 19(16): 4383-92.
[21]
Li J, Buchner J. Structure, function and regulation of the hsp90 machinery. Biomed J 2013; 36(3): 106-17.
[22]
Schopf FH, Biebl MM, Buchner J. The HSP90 chaperone machinery. Nat Rev Mol Cell Biol 2017; 18(6): 345-60.
[23]
Ebong IO, Morgner N, Zhou M, et al. Heterogeneity and dynamics in the assembly of the heat shock protein 90 chaperone complexes. Proc Natl Acad Sci USA 2011; 108(44): 17939-44.
[24]
Röhl A, Rohrberg J, Buchner J. The chaperone Hsp90: changing partners for demanding clients. Trends Biochem Sci 2013; 38(5): 253-62.
[25]
Ambati SR, Lopes EC, Kosugi K, et al. Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma. Mol Oncol 2014; 8(2): 323-36.
[26]
Chiosis G, Dickey CA, Johnson JL. A global view of Hsp90 functions. Nat Struct Mol Biol 2013; 20(1): 1-4.
[27]
Sahasrabudhe P, Rohrberg J, Biebl MM, Rutz DA, Buchner J. The Plasticity of the Hsp90 Co-chaperone System. Mol Cell 2017; 67(6): 947-961.e5.
[28]
Sanchez ER, Toft DO, Schlesinger MJ, Pratt WB. Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein. J Biol Chem 1985; 260(23): 12398-401.
[29]
Criado-Marrero M, Rein T, Binder EB, Porter JT, Koren J III, Blair LJ. Hsp90 and FKBP51: complex regulators of psychiatric diseases. Philos Trans R Soc Lond B Biol Sci 2018; 373(1738): 373.
[30]
Azoitei N, Diepold K, Brunner C, et al. HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization. Cancer Res 2014; 74(23): 7125-36.
[31]
Hessling M, Richter K, Buchner J. Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90. Nat Struct Mol Biol 2009; 16(3): 287-93.
[32]
Fukuyo Y, Hunt CR, Horikoshi N. Geldanamycin and its anti-cancer activities. Cancer Lett 2010; 290(1): 24-35.
[33]
Spiegelberg D, Dascalu A, Mortensen AC, et al. The novel HSP90 inhibitor AT13387 potentiates radiation effects in squamous cell carcinoma and adenocarcinoma cells. Oncotarget 2015; 6(34): 35652-66.
[34]
Karagöz GE, Rüdiger SG. Hsp90 interaction with clients. Trends Biochem Sci 2015; 40(2): 117-25.
[35]
Zhou CC, Yang F, Yuan SX, et al. Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma. Hepatology 2016; 63(3): 850-63.
[36]
Guo H, Zhao L, Shi B, et al. GALNT5 uaRNA promotes gastric cancer progression through its interaction with HSP90. Oncogene 2018; 37(33): 4505-17.
[37]
Takeuchi T, Suzuki M, Fujikake N, et al. Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. Proc Natl Acad Sci USA 2015; 112(19): E2497-506.
[38]
Wong DS, Jay DG. Emerging Roles of Extracellular Hsp90 in Cancer. Adv Cancer Res 2016; 129: 141-63.
[39]
Woodford MR, Dunn D, Miller JB, Jamal S, Neckers L, Mollapour M. Impact of Posttranslational Modifications on the Anticancer Activity of Hsp90 Inhibitors. Adv Cancer Res 2016; 129: 31-50.
[40]
Wang Y, Koay YC, McAlpine SR. How Selective are Hsp90 Inhibitors for Cancer Cells over Normal Cells? ChemMedChem 2017; 12(5): 353-7.
[41]
Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003; 425(6956): 407-10.
[42]
Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 1997; 89(2): 239-50.
[43]
Ghadban T, Jessen A, Reeh M, et al. In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines. Int J Mol Med 2016; 38(4): 1296-302.
[44]
Krishnamoorthy GP, Guida T, Alfano L, et al. Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation. J Biol Chem 2013; 288(24): 17481-94.
[45]
Sharp S, Workman P. Inhibitors of the HSP90 molecular chaperone: current status. Adv Cancer Res 2006; 95: 323-48.
[46]
Smith V, Sausville EA, Camalier RF, Fiebig HH, Burger AM. Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygel-danamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Cancer Chemother Pharmacol 2005; 56(2): 126-37.
[47]
Leng AM, Liu T, Yang J, et al. The apoptotic effect and associated signalling of HSP90 inhibitor 17-DMAG in hepatocellular carcinoma cells. Cell Biol Int 2012; 36(10): 893-9.
[48]
Egorin MJ, Lagattuta TF, Hamburger DR, et al. Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethyl-amino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats. Cancer Chemother Pharmacol 2002; 49(1): 7-19.
[49]
Palacios C, Martín-Pérez R, López-Pérez AI, Pandiella A, López-Rivas A. Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. Leuk Res 2010; 34(11): 1533-8.
[50]
Chang YJ, Huang CY, Hung CS, Liu HH, Wei PL. Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in colon cancer cells. Tumour Biol 2015; 36(6): 4367-76.
[51]
Wang Y, McAlpine SR. Regulating the cytoprotective response in cancer cells using simultaneous inhibition of Hsp90 and Hsp70. Org Biomol Chem 2015; 13(7): 2108-16.
[52]
Brough PA, Aherne W, Barril X, et al. 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J Med Chem 2008; 51(2): 196-218.
[53]
Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID. Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol 2016; 13(6): 361-9.
[54]
Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012; 486(7404): 532-6.
[55]
Azoitei N, Hoffmann CM, Ellegast JM, et al. Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med 2012; 209(4): 697-711.
[56]
Cercek A, Shia J, Gollub M, et al. Ganetespib, a novel Hsp90 inhibitor in patients with KRAS mutated and wild type, refractory metastatic colorectal cancer. Clin Colorectal Cancer 2014; 13(4): 207-12.
[57]
Wang CY, Guo ST, Wang JY, et al. Inhibition of HSP90 by AUY922 Preferentially Kills Mutant KRAS Colon Cancer Cells by Activating Bim through ER Stress. Mol Cancer Ther 2016; 15(3): 448-59.
[58]
Lee DH, Sung KS, Bartlett DL, Kwon YT, Lee YJ. HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells. Cell Signal 2015; 27(2): 293-305.
[59]
Shah T, Hochhauser D, Frow R, Quaglia A, Dhillon AP, Caplin ME. Epidermal growth factor receptor expression and activation in neuroendocrine tumours. J Neuroendocrinol 2006; 18(5): 355-60.
[60]
Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 2010; 10(8): 537-49.
[61]
Zitzmann K, Ailer G, Vlotides G, et al. Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells. Int J Oncol 2013; 43(6): 1824-32.
[62]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[63]
Bao XH, Takaoka M, Hao HF, et al. Antiproliferative effect of the HSP90 inhibitor NVP-AUY922 is determined by the expression of PTEN in esophageal cancer. Oncol Rep 2013; 29(1): 45-50.
[64]
Slotta-Huspenina J, Berg D, Bauer K, et al. Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas. PLoS One 2012; 7(7): e41420.
[65]
Djuzenova CS, Blassl C, Roloff K, et al. Hsp90 inhibitor NVP-AUY922 enhances radiation sensitivity of tumor cell lines under hypoxia. Cancer Biol Ther 2012; 13(6): 425-34.
[66]
Kang J, Sergio CM, Sutherland RL, Musgrove EA. Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells. BMC Cancer 2014; 14: 32.
[67]
Yaglom JA, Gabai VL, Sherman MY. High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways. Cancer Res 2007; 67(5): 2373-81.
[68]
Breinig M, Caldas-Lopes E, Goeppert B, et al. Targeting heat shock protein 90 with non-quinone inhibitors: a novel chemotherapeutic approach in human hepatocellular carcinoma. Hepatology 2009; 50(1): 102-12.
[69]
Gallerne C, Prola A, Lemaire C. Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Biochim Biophys Acta 2013; 1833(6): 1356-66.
[70]
Liu H, Chiang MY, Pear WS. Critical roles of NOTCH1 in acute T-cell lymphoblastic leukemia. Int J Hematol 2011; 94(2): 118-25.
[71]
Weng AP, Millholland JM, Yashiro-Ohtani Y, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006; 20(15): 2096-109.
[72]
Wang Z, Hu Y, Xiao D, et al. Stabilization of Notch1 by the Hsp90 chaperone is crucial for T-cell leukemogenesis. Clin Cancer Res 2017; 23(14): 3834-46.
[73]
Smyth T, Paraiso KHT, Hearn K, et al. Inhibition of HSP90 by AT13387 delays the emergence of resistance to BRAF inhibitors and overcomes resistance to dual BRAF and MEK inhibition in melanoma models. Mol Cancer Ther 2014; 13(12): 2793-804.
[74]
Mahendrarajah N, Borisova ME, Reichardt S, et al. HSP90 is necessary for the ACK1-dependent phosphorylation of STAT1 and STAT3. Cell Signal 2017; 39: 9-17.
[75]
Ferraldeschi R, Welti J, Powers MV, et al. Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. Cancer Res 2016; 76(9): 2731-42.
[76]
Sun Y, Huang YH, Huang FY, et al. 3′-epi-12β-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells. Theranostics 2018; 8(7): 2044-60.
[77]
Moore J, Megaly M, MacNeil AJ, Klentrou P, Tsiani E. Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells. Biomed Pharmacother Biomed Pharmacother 2016; 83: 725-32.
[78]
Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000; 103(2): 253-62.

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