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Review Open Access

HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)

  • Authors:
    • Zi-Nan Li
    • Ying Luo
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 6
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    Published online on: November 9, 2022
       https://doi.org/10.3892/or.2022.8443
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Abstract

Heat shock protein 90 (HSP90) is a vital chaperone protein, regulating signaling pathways and correcting misfolded proteins in cancer cells by interacting with oncogenic client proteins and co‑chaperones. The inhibition of HSP90 chaperone machinery has been demonstrated as a potential approach with which to inhibit tumor survival, proliferation, invasion and migration. Numerous HSP90 inhibitors have been reported and have exhibited value as cancer‑targeted therapies by interrupting the ATPase activity of HSP90, thus suppressing the oncogenic pathways in cancer cells. These inhibitors have been classified into three categories: i) N‑terminal domain (NTD) inhibitors; ii) C‑terminal domain (CTD) inhibitors; and iii) isoform‑selective inhibitors. However, none of these HSP90 inhibitors are used as clinical treatments. The major limiting factors can be summarized into drug resistance, dose‑limiting toxicity and poor pharmacokinetic profiles. Novel HSP90‑targeted compounds are constantly being discovered and tested for their antitumor efficacy in preclinical and clinical trials, highlighting the prospect of the use of HSP90 inhibitors as cancer‑targeted therapies. Additionally, improved antitumor effects have been observed when HSP90 inhibitors are used in combination with chemotherapy, targeted agents, or immunotherapy. In the present review, the effects of HSP90 inhibitors on the management of the cancer process are discussed and previous and novel HSP90‑based therapeutic strategies in cancer treatment are summarized. Furthermore, prospective HSP90‑targeting candidates are proposed for their future evaluation as cancer treatments.
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1 

Condelli V, Crispo F, Pietrafesa M, Lettini G, Matassa DS, Esposito F, Landriscina M and Maddalena F: HSP90 molecular chaperones, metabolic rewiring, and epigenetics: Impact on tumor progression and perspective for anticancer therapy. Cells. 8:5322019. View Article : Google Scholar : PubMed/NCBI

2 

Hoter A, El-Sabban ME and Naim HY: The HSP90 family: Structure, regulation, function, and implications in health and disease. Int J Mol Sci. 19:25602018. View Article : Google Scholar : PubMed/NCBI

3 

Whitesell L and Lindquist SL: HSP90 and the chaperoning of cancer. Nat Rev Cancer. 5:761–772. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Zhang H and Burrows F: Targeting multiple signal transduction pathways through inhibition of Hsp90. J Mol Med (Berl). 82:488–499. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Chiosis G: Targeting chaperones in transformed systems-a focus on HSP90 and cancer. Expert Opin Ther Targets. 10:37–50. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Workman P: Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Lett. 206:149–157. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Csermely P, Schnaider T, Soti C, Prohaszka Z and Nardai G: The 90-kDa molecular chaperone family: Structure, function, and clinical applications. A comprehensive review. Pharmacol Ther. 79:129–168. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW and Pearl LH: Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell. 90:65–75. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW and Pearl LH: Structural and functional analysis of the middle segment of hsp90: Implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell. 11:647–658. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Minami Y, Kimura Y, Kawasaki H, Suzuki K and Yahara I: The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo. Mol Cell Biol. 14:1459–1464. 1994. View Article : Google Scholar : PubMed/NCBI

11 

Panaretou B, Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW and Pearl LH: ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J. 17:4829–4836. 1998. View Article : Google Scholar : PubMed/NCBI

12 

Vorherr T, Knopfel L, Hofmann F, Mollner S, Pfeuffer T and Carafoli E: The calmodulin binding domain of nitric oxide synthase and adenylyl cyclase. Biochemistry. 32:6081–6088. 1993. View Article : Google Scholar : PubMed/NCBI

13 

Jackson SE: Hsp90: Structure and function. Top Curr Chem. 328:155–240. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Li J, Soroka J and Buchner J: The Hsp90 chaperone machinery: Conformational dynamics and regulation by co-chaperones. Biochim Biophys Acta. 1823:624–635. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Marzec M, Eletto D and Argon Y: GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. Biochim Biophys Acta. 1823:774–787. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Amoroso MR, Matassa DS, Sisinni L, Lettini G, Landriscina M and Esposito F: TRAP1 revisited: Novel localizations and functions of a ‘next-generation’ biomarker (review). Int J Oncol. 45:969–977. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Soga S, Akinaga S and Shiotsu Y: Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Curr Pharm Des. 19:366–376. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Sanchez J, Carter TR, Cohen MS and Blagg BSJ: Old and new approaches to target the Hsp90 chaperone. Curr Cancer Drug Targets. 20:253–270. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Koren J III and Blagg BSJ: The right tool for the job: An overview of Hsp90 inhibitors. Adv Exp Med Biol. 1243:135–146. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Jhaveri K, Taldone T, Modi S and Chiosis G: Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta. 1823:742–755. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Dutta R and Inouye M: GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci. 25:24–28. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Meng X, Devin J, Sullivan WP, Toft D, Baulieu EE and Catelli MG: Mutational analysis of Hsp90 alpha dimerization and subcellular localization: Dimer disruption does not impede ‘in vivo’ interaction with estrogen receptor. J Cell Sci. 109:1677–1687. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Soti C, Vermes A, Haystead TA and Csermely P: Comparative analysis of the ATP-binding sites of Hsp90 by nucleotide affinity cleavage: A distinct nucleotide specificity of the C-terminal ATP-binding site. Eur J Biochem. 270:2421–2428. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Sreedhar AS, Kalmar E, Csermely P and Shen YF: Hsp90 isoforms: Functions, expression and clinical importance. FEBS Lett. 562:11–15. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Tsutsumi S, Mollapour M, Prodromou C, Lee CT, Panaretou B, Yoshida S, Mayer MP and Neckers LM: Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. Proc Natl Acad Sci USA. 109:2937–2942. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Rowlands M, McAndrew C, Prodromou C, Pearl L, Kalusa A, Jones K, Workman P and Aherne W: Detection of the ATPase activity of the molecular chaperones Hsp90 and Hsp72 using the TranscreenerTM ADP assay kit. J Biomol Screen. 15:279–286. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Wandinger SK, Richter K and Buchner J: The Hsp90 chaperone machinery. J Biol Chem. 283:18473–18477. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C and Pearl LH: Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature. 440:1013–1017. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Richter K, Soroka J, Skalniak L, Leskovar A, Hessling M, Reinstein J and Buchner J: Conserved conformational changes in the ATPase cycle of human Hsp90. J Biol Chem. 283:17757–17765. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Terasawa K, Minami M and Minami Y: Constantly updated knowledge of Hsp90. J Biochem. 137:443–447. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Meyer P, Prodromou C, Liao C, Hu B, Roe SM, Vaughan CK, Vlasic I, Panaretou B, Piper PW and Pearl LH: Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO J. 23:1402–1410. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Langer T, Rosmus S and Fasold H: Intracellular localization of the 90 kDA heat shock protein (HSP90alpha) determined by expression of a EGFP-HSP90alpha-fusion protein in unstressed and heat stressed 3T3 cells. Cell Biol Int. 27:47–52. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Wang X, Song X, Zhuo W, Fu Y, Shi H, Liang Y, Tong M, Chang G and Luo Y: The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proc Natl Acad Sci USA. 106:21288–21293. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Sidera K, Samiotaki M, Yfanti E, Panayotou G and Patsavoudi E: Involvement of cell surface HSP90 in cell migration reveals a novel role in the developing nervous system. J Biol Chem. 279:45379–45388. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Tsutsumi S and Neckers L: Extracellular heat shock protein 90: A role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci. 98:1536–1539. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Stellas D, Karameris A and Patsavoudi E: Monoclonal antibody 4C5 immunostains human melanomas and inhibits melanoma cell invasion and metastasis. Clin Cancer Res. 13:1831–1838. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Eletto D, Dersh D and Argon Y: GRP94 in ER quality control and stress responses. Semin Cell Dev Biol. 21:479–485. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Hua G, Zhang Q and Fan Z: Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J Biol Chem. 282:20553–20560. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Sciacovelli M, Guzzo G, Morello V, Frezza C, Zheng L, Nannini N, Calabrese F, Laudiero G, Esposito F, Landriscina M, et al: The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. Cell Metab. 17:988–999. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Masgras I, Sanchez-Martin C, Colombo G and Rasola A: The chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells. Front Oncol. 7:582017. View Article : Google Scholar : PubMed/NCBI

41 

Zhao R, Davey M, Hsu YC, Kaplanek P, Tong A, Parsons AB, Krogan N, Cagney G, Mai D, Greenblatt J, et al: Navigating the chaperone network: An integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell. 120:715–727. 2005. View Article : Google Scholar : PubMed/NCBI

42 

Pratt WB, Morishima Y and Osawa Y: The Hsp90 chaperone machinery regulates signaling by modulating ligand binding clefts. J Biol Chem. 283:22885–22889. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Zuehlke A and Johnson JL: Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers. 93:211–217. 2010. View Article : Google Scholar : PubMed/NCBI

44 

Diaz-Villanueva JF, Diaz-Molina R and Garcia-Gonzalez V: Protein folding and mechanisms of proteostasis. Int J Mol Sci. 16:17193–17230. 2015. View Article : Google Scholar : PubMed/NCBI

45 

Pearl LH, Prodromou C and Workman P: The Hsp90 molecular chaperone: An open and shut case for treatment. Biochem J. 410:439–453. 2008. View Article : Google Scholar : PubMed/NCBI

46 

Trepel J, Mollapour M, Giaccone G and Neckers L: Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer. 10:537–549. 2010. View Article : Google Scholar : PubMed/NCBI

47 

Neckers L and Workman P: Hsp90 molecular chaperone inhibitors: Are we there yet? Clin Cancer Res. 18:64–76. 2012. View Article : Google Scholar : PubMed/NCBI

48 

Garg G, Khandelwal A and Blagg BS: Anticancer inhibitors of Hsp90 function: Beyond the usual suspects. Adv Cancer Res. 129:51–88. 2016. View Article : Google Scholar : PubMed/NCBI

49 

Neckers L, Mimnaugh E and Schulte TW: Hsp90 as an anti-cancer target. Drug Resist Updat. 2:165–172. 1999. View Article : Google Scholar : PubMed/NCBI

50 

Modi S, Stopeck A, Linden H, Solit D, Chandarlapaty S, Rosen N, D'Andrea G, Dickler M, Moynahan ME, Sugarman S, et al: HSP90 inhibition is effective in breast cancer: A phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 17:5132–5139. 2011. View Article : Google Scholar : PubMed/NCBI

51 

Ishikawa Y, Kozakai T, Morita H, Saida K, Oka S and Masuo Y: Rapid detection of mycoplasma contamination in cell cultures using SYBR Green-based real-time polymerase chain reaction. In Vitro Cell Dev Biol Anim. 42:63–69. 2006. View Article : Google Scholar : PubMed/NCBI

52 

Miyata Y, Nakamoto H and Neckers L: The therapeutic target Hsp90 and cancer hallmarks. Curr Pharm Des. 19:347–365. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Barrott JJ and Haystead TA: Hsp90, an unlikely ally in the war on cancer. FEBS J. 280:1381–1396. 2013. View Article : Google Scholar : PubMed/NCBI

54 

Mori M, Hitora T, Nakamura O, Yamagami Y, Horie R, Nishimura H and Yamamoto T: Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells. Int J Oncol. 46:47–54. 2015. View Article : Google Scholar : PubMed/NCBI

55 

Ciocca DR and Calderwood SK: Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 10:86–103. 2005. View Article : Google Scholar : PubMed/NCBI

56 

Jafari A, Rezaei-Tavirani M, Farhadihosseinabadi B, Taranejoo S and Zali H: HSP90 and Co-chaperones: Impact on tumor progression and prospects for molecular-targeted cancer therapy. Cancer Invest. 38:310–328. 2020. View Article : Google Scholar : PubMed/NCBI

57 

Birbo B, Madu EE, Madu CO, Jain A and Lu Y: Role of HSP90 in cancer. Int J Mol Sci. 22:103172021. View Article : Google Scholar : PubMed/NCBI

58 

Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL and Kluger HM: High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 67:2932–2937. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Cheng Q, Chang JT, Geradts J, Neckers LM, Haystead T, Spector NL and Lyerly HK: Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer. Breast Cancer Res. 14:R622012. View Article : Google Scholar : PubMed/NCBI

60 

Moran Luengo T, Mayer MP and Rudiger SGD: The Hsp70-Hsp90 chaperone cascade in protein folding. Trends Cell Biol. 29:164–177. 2019. View Article : Google Scholar : PubMed/NCBI

61 

Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC and Burrows FJ: A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 425:407–410. 2003. View Article : Google Scholar : PubMed/NCBI

62 

Moulick K, Ahn JH, Zong H, Rodina A, Cerchietti L, Gomes DaGama EM, Caldas-Lopes E, Beebe K, Perna F, Hatzi K, et al: Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nat Chem Biol. 7:818–826. 2011. View Article : Google Scholar : PubMed/NCBI

63 

Ferrarini M, Heltai S, Zocchi MR and Rugarli C: Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer. 51:613–619. 1992. View Article : Google Scholar : PubMed/NCBI

64 

Sims JD, McCready J and Jay DG: Extracellular heat shock protein (Hsp)70 and Hsp90alpha assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS One. 6:e188482011. View Article : Google Scholar : PubMed/NCBI

65 

Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, Bright AM, Yerushalmi D, Liang M, Chen M, et al: Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: Using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing. Mol Cell Biol. 28:3344–3358. 2008. View Article : Google Scholar : PubMed/NCBI

66 

Eustace BK, Sakurai T, Stewart JK, Yimlamai D, Unger C, Zehetmeier C, Lain B, Torella C, Henning SW, Beste G, et al: Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol. 6:507–514. 2004. View Article : Google Scholar : PubMed/NCBI

67 

Gorska M, Popowska U, Sielicka-Dudzin A, Kuban-Jankowska A, Sawczuk W, Knap N, Cicero G and Wozniak F: Geldanamycin and its derivatives as Hsp90 inhibitors. Front Biosci (Landmark Ed). 17:2269–2277. 2012. View Article : Google Scholar : PubMed/NCBI

68 

Samuni Y, Ishii H, Hyodo F, Samuni U, Krishna MC, Goldstein S and Mitchell JB: Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs. Free Radic Biol Med. 48:1559–1563. 2010. View Article : Google Scholar : PubMed/NCBI

69 

Biamonte MA, Van de Water R, Arndt JW, Scannevin RH, Perret D and Lee WC: Heat shock protein 90: Inhibitors in clinical trials. J Med Chem. 53:3–17. 2010. View Article : Google Scholar : PubMed/NCBI

70 

Ronnen EA, Kondagunta GV, Ishill N, Sweeney SM, Deluca JK, Schwartz L, Bacik J and Motzer RJ: A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma. Invest New Drugs. 24:543–546. 2006. View Article : Google Scholar : PubMed/NCBI

71 

Solit DB, Osman I, Polsky D, Panageas KS, Daud A, Goydos JS, Teitcher J, Wolchok JD, Germino FJ, Krown SE, et al: Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin Cancer Res. 14:8302–8307. 2008. View Article : Google Scholar : PubMed/NCBI

72 

Heath EI, Hillman DW, Vaishampayan U, Sheng S, Sarkar F, Harper F, Gaskins M, Pitot HC, Tan W, Ivy SP, et al: A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 14:7940–7946. 2008. View Article : Google Scholar : PubMed/NCBI

73 

Hanson BE and Vesole DH: Retaspimycin hydrochloride (IPI-504): A novel heat shock protein inhibitor as an anticancer agent. Expert Opin Investig Drugs. 18:1375–1383. 2009. View Article : Google Scholar : PubMed/NCBI

74 

Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, Neckers L and Trepel JB: Update on Hsp90 inhibitors in clinical trial. Curr Top Med Chem. 9:1479–1492. 2009. View Article : Google Scholar : PubMed/NCBI

75 

Wagner AJ, Chugh R, Rosen LS, Morgan JA, George S, Gordon M, Dunbar J, Normant E, Grayzel D and Demetri GD: A phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas. Clin Cancer Res. 19:6020–6029. 2013. View Article : Google Scholar : PubMed/NCBI

76 

Floris G, Sciot R, Wozniak A, Van Looy T, Wellens J, Faa G, Normant E, Debiec-Rychter M and Schoffski P: The Novel HSP90 inhibitor, IPI-493, is highly effective in human gastrostrointestinal stromal tumor xenografts carrying heterogeneous KIT mutations. Clin Cancer Res. 17:5604–5614. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Mellatyar H, Talaei S, Pilehvar-Soltanahmadi Y, Barzegar A, Akbarzadeh A, Shahabi A, Barekati-Mowahed M and Zarghami N: Targeted cancer therapy through 17-DMAG as an Hsp90 inhibitor: Overview and current state of the art. Biomed Pharmacother. 102:608–617. 2018. View Article : Google Scholar : PubMed/NCBI

78 

Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, et al: Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms. Chem Biol. 11:775–785. 2004. View Article : Google Scholar : PubMed/NCBI

79 

Lundgren K, Zhang H, Brekken J, Huser N, Powell RE, Timple N, Busch DJ, Neely L, Sensintaffar JL, Yang YC, et al: BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol Cancer Ther. 8:921–929. 2009. View Article : Google Scholar : PubMed/NCBI

80 

Dickson MA, Okuno SH, Keohan ML, Maki RG, D'Adamo DR, Akhurst TJ, Antonescu CR and Schwartz GK: Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors. Ann Oncol. 24:252–257. 2013. View Article : Google Scholar : PubMed/NCBI

81 

Yan L, Zhang W, Zhang B, Xuan C and Wang D: BIIB021: A novel inhibitor to heat shock protein 90-addicted oncology. Tumour Biol. 39:10104283176983552017. View Article : Google Scholar : PubMed/NCBI

82 

Hong D, Said R, Falchook G, Naing A, Moulder S, Tsimberidou AM, Galluppi G, Dakappagari N, Storgard C, Kurzrock R and Rosen LS: Phase I study of BIIB028, a selective heat shock protein 90 inhibitor, in patients with refractory metastatic or locally advanced solid tumors. Clin Cancer Res. 19:4824–4831. 2013. View Article : Google Scholar : PubMed/NCBI

83 

Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y, et al: Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci USA. 106:8368–8373. 2009. View Article : Google Scholar : PubMed/NCBI

84 

Cerchietti LC, Lopes EC, Yang SN, Hatzi K, Bunting KL, Tsikitas LA, Mallik A, Robles AI, Walling J, Varticovski L, et al: A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat Med. 15:1369–1376. 2009. View Article : Google Scholar : PubMed/NCBI

85 

Ambati SR, Lopes EC, Kosugi K, Mony U, Zehir A, Shah SK, Taldone T, Moreira AL, Meyers PA, Chiosis G, et al: Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma. Mol Oncol. 8:323–336. 2014. View Article : Google Scholar : PubMed/NCBI

86 

Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, Hu M, Partridge JM, Rice J, Scott A, et al: Application of chemoproteomics to drug discovery: Identification of a clinical candidate targeting hsp90. Chem Biol. 17:686–694. 2010. View Article : Google Scholar : PubMed/NCBI

87 

Huang KH, Veal JM, Fadden RP, Rice JW, Eaves J, Strachan JP, Barabasz AF, Foley BE, Barta TE, Ma W, et al: Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J Med Chem. 52:4288–4305. 2009. View Article : Google Scholar : PubMed/NCBI

88 

Cheung KM, Matthews TP, James K, Rowlands MG, Boxall KJ, Sharp SY, Maloney A, Roe SM, Prodromou C, Pearl LH, et al: The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors. Bioorg Med Chem Lett. 15:3338–3343. 2005. View Article : Google Scholar : PubMed/NCBI

89 

Brough PA, Aherne W, Barril X, Borgognoni J, Boxall K, Cansfield JE, Cheung KM, Collins I, Davies NG, Drysdale MJ, et al: 4,5-diarylisoxazole Hsp90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer. J Med Chem. 51:196–218. 2008. View Article : Google Scholar : PubMed/NCBI

90 

Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, Patterson L, de Haven Brandon A, Gowan S, Boxall F, et al: NVP-AUY922: A novel heat shock protein 90 inhibitor active against xenograft tumor growth angiogenesis, and metastasis. Cancer Res. 68:2850–2860. 2008. View Article : Google Scholar : PubMed/NCBI

91 

Jensen MR, Schoepfer J, Radimerski T, Massey A, Guy CT, Brueggen J, Quadt C, Buckler A, Cozens R, Drysdale MJ, et al: NVP-AUY922: A small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res. 10:R332008. View Article : Google Scholar : PubMed/NCBI

92 

Murray CW, Carr MG, Callaghan O, Chessari G, Congreve M, Cowan S, Coyle JE, Downham R, Figueroa E, Frederickson M, et al: Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency. J Med Chem. 53:5942–5955. 2010. View Article : Google Scholar : PubMed/NCBI

93 

Wang Y, Trepel JB, Neckers LM and Giaccone G: STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs. 11:1466–1476. 2010.PubMed/NCBI

94 

Nakashima T, Ishii T, Tagaya H, Seike T, Nakagawa H, Kanda Y, Akinaga S, Soga S and Shiotsu Y: New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res. 16:2792–2802. 2010. View Article : Google Scholar : PubMed/NCBI

95 

Cavenagh J, Oakervee H, Baetiong-Caguioa P, Davies F, Gharibo M, Rabin N, Kurman M, Novak B, Shiraishi N, Nakashima D, et al: A phase I/II study of KW-2478, an Hsp90 inhibitor, in combination with bortezomib in patients with relapsed/refractory multiple myeloma. Br J Cancer. 117:1295–1302. 2017. View Article : Google Scholar : PubMed/NCBI

96 

Chang X, Zhao X, Wang J, Ding S, Xiao L, Zhao E and Zheng X: Effect of Hsp90 inhibitor KW-2478 on HepG2 cells. Anticancer Agents Med Chem. 19:2231–2242. 2019. View Article : Google Scholar : PubMed/NCBI

97 

Yong K, Cavet J, Johnson P, Morgan G, Williams C, Nakashima D, Akinaga S, Oakervee H and Cavenagh J: Phase I study of KW-2478, a novel Hsp90 inhibitor, in patients with B-cell malignancies. Br J Cancer. 114:7–13. 2016. View Article : Google Scholar : PubMed/NCBI

98 

Huang W, Ye M, Zhang LR, Wu QD, Zhang M, Xu JH and Zheng W: FW-04-806 inhibits proliferation and induces apoptosis in human breast cancer cells by binding to N-terminus of Hsp90 and disrupting Hsp90-Cdc37 complex formation. Mol Cancer. 13:1502014. View Article : Google Scholar : PubMed/NCBI

99 

Huang W, Wu QD, Zhang M, Kong YL, Cao PR, Zheng W, Xu JH and Ye M: Novel Hsp90 inhibitor FW-04-806 displays potent antitumor effects in HER2-positive breast cancer cells as a single agent or in combination with lapatinib. Cancer Lett. 356:862–871. 2015. View Article : Google Scholar : PubMed/NCBI

100 

Suda A, Koyano H, Hayase T, Hada K, Kawasaki K, Komiyama S, Hasegawa K, Fukami TA, Sato S, Miura T, et al: Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors. Bioorg Med Chem Lett. 22:1136–1141. 2012. View Article : Google Scholar : PubMed/NCBI

101 

Bussenius J, Blazey CM, Aay N, Anand NK, Arcalas A, Baik T, Bowles OJ, Buhr CA, Costanzo S, Curtis JK, et al: Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 22:5396–5404. 2012. View Article : Google Scholar : PubMed/NCBI

102 

Samarasinghe B, Wales CT, Taylor FR and Jacobs AT: Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1 expression and promotion of autophagic flux. Biochem Pharmacol. 87:445–455. 2014. View Article : Google Scholar : PubMed/NCBI

103 

Soti C, Racz A and Csermely P: A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J Biol Chem. 277:7066–7075. 2002. View Article : Google Scholar : PubMed/NCBI

104 

Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D and Neckers LM: Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones. 3:100–108. 1998. View Article : Google Scholar : PubMed/NCBI

105 

Donnelly A and Blagg BS: Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket. Curr Med Chem. 15:2702–2717. 2008. View Article : Google Scholar : PubMed/NCBI

106 

Buchner J: Bacterial Hsp90-desperately seeking clients. Mol Microbiol. 76:540–544. 2010. View Article : Google Scholar : PubMed/NCBI

107 

Yun BG, Huang W, Leach N, Hartson SD and Matts RL: Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions. Biochemistry. 43:8217–8229. 2004. View Article : Google Scholar : PubMed/NCBI

108 

Zhao J, Zhao H, Hall JA, Brown D, Brandes E, Bazzill J, Grogan PT, Subramanian C, Vielhauer G, Cohen MS and Blagg BS: Triazole containing novobiocin and biphenyl amides as Hsp90 C-Terminal inhibitors. Medchemcomm. 5:1317–1323. 2014. View Article : Google Scholar : PubMed/NCBI

109 

Astl L, Stetz G and Verkhivker GM: Dissecting molecular principles of the Hsp90 chaperone regulation by allosteric modulators using a hierarchical simulation approach and network modeling of allosteric interactions: Conformational selection dictates the diversity of protein responses and ligand-specific functional mechanisms. J Chem Theory Comput. 16:6656–6677. 2020. View Article : Google Scholar : PubMed/NCBI

110 

Marcu MG, Chadli A, Bouhouche I, Catelli M and Neckers LM: The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J Biol Chem. 275:37181–37186. 2000. View Article : Google Scholar : PubMed/NCBI

111 

Forsberg LK, Anyika M, You Z, Emery S, McMullen M, Dobrowsky RT and Blagg BSJ: Development of noviomimetics that modulate molecular chaperones and manifest neuroprotective effects. Eur J Med Chem. 143:1428–1435. 2018. View Article : Google Scholar : PubMed/NCBI

112 

Kumar Mv V, Ebna Noor R, Davis RE, Zhang Z, Sipavicius E, Keramisanou D, Blagg BSJ and Gelis I: Molecular insights into the interaction of Hsp90 with allosteric inhibitors targeting the C-terminal domain. Medchemcomm. 9:1323–1331. 2018. View Article : Google Scholar : PubMed/NCBI

113 

Rahimi MN and McAlpine SR: Protein-protein inhibitor designed de novo to target the MEEVD region on the C-terminus of Hsp90 and block co-chaperone activity. Chem Commun (Camb). 55:846–849. 2019. View Article : Google Scholar : PubMed/NCBI

114 

Huo Y, Buckton LK, Bennett JL, Smith EC, Byrne FL, Hoehn KL, Rahimi MN and McAlpine SR: Delivering bioactive cyclic peptides that target Hsp90 as prodrugs. J Enzyme Inhib Med Chem. 34:728–739. 2019. View Article : Google Scholar : PubMed/NCBI

115 

Rahimi MN, Foster HG, Farazi SN, Chapman R and McAlpine SR: Polymer mediated transport of the Hsp90 inhibitor LB76, a polar cyclic peptide, produces an Hsp90 cellular phenotype. Chem Commun (Camb). 55:4515–4518. 2019. View Article : Google Scholar : PubMed/NCBI

116 

Subramanian C, Grogan PT, Wang T, Bazzill J, Zuo A, White PT, Kalidindi A, Kuszynski D, Wang G, Blagg BSJ and Cohen MS: Novel C-terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self-renewal, and epithelial-mesenchymal transition. Mol Oncol. 14:2058–2068. 2020. View Article : Google Scholar : PubMed/NCBI

117 

Subramanian C, Kovatch KJ, Sim MW, Wang G, Prince ME, Carey TE, Davis R, Blagg BSJ and Cohen MS: Novel C-Terminal heat shock protein 90 inhibitors (KU711 and Ku757) are effective in targeting head and neck squamous cell carcinoma cancer stem cells. Neoplasia. 19:1003–1011. 2017. View Article : Google Scholar : PubMed/NCBI

118 

White PT, Subramanian C, Zhu Q, Zhang H, Zhao H, Gallagher R, Timmermann BN, Blagg BS and Cohen MS: Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery. 159:142–151. 2016. View Article : Google Scholar : PubMed/NCBI

119 

Samadi AK, Zhang X, Mukerji R, Donnelly AC, Blagg BS and Cohen MS: A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells. Cancer Lett. 312:158–167. 2011. View Article : Google Scholar : PubMed/NCBI

120 

Shelton SN, Shawgo ME, Matthews SB, Lu Y, Donnelly AC, Szabla K, Tanol M, Vielhauer GA, Rajewski RA, Matts RL, et al: KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells. Mol Pharmacol. 76:1314–1322. 2009. View Article : Google Scholar : PubMed/NCBI

121 

Nirmalanandhan VS, Duren A, Hendricks P, Vielhauer G and Sittampalam GS: Activity of anticancer agents in a three-dimensional cell culture model. Assay Drug Dev Technol. 8:581–590. 2010. View Article : Google Scholar : PubMed/NCBI

122 

Cohen SM, Mukerji R, Samadi AK, Zhang X, Zhao H, Blagg BS and Cohen MS: Novel C-terminal Hsp90 inhibitor for head and neck squamous cell cancer (HNSCC) with in vivo efficacy and improved toxicity profiles compared with standard agents. Ann Surg Oncol. 19 (Suppl 3):S483–S490. 2012. View Article : Google Scholar : PubMed/NCBI

123 

Hyun SY, Le HT, Nguyen CT, Yong YS, Boo HJ, Lee HJ, Lee JS, Min HY, Ann J, Chen J, et al: Development of a novel Hsp90 inhibitor NCT-50 as a potential anticancer agent for the treatment of non-small cell lung cancer. Sci Rep. 8:139242018. View Article : Google Scholar : PubMed/NCBI

124 

Li W, Sahu D and Tsen F: Secreted heat shock protein-90 (Hsp90) in wound healing and cancer. Biochim Biophys Acta. 1823:730–741. 2012. View Article : Google Scholar : PubMed/NCBI

125 

Biswas C, Ostrovsky O, Makarewich CA, Wanderling S, Gidalevitz T and Argon Y: The peptide-binding activity of GRP94 is regulated by calcium. Biochem J. 405:233–241. 2007. View Article : Google Scholar : PubMed/NCBI

126 

Ernst JT, Liu M, Zuccola H, Neubert T, Beaumont K, Turnbull A, Kallel A, Vought B and Stamos D: Correlation between chemotype-dependent binding conformations of HSP90α/β and isoform selectivity-Implications for the structure-based design of HSP90α/β selective inhibitors for treating neurodegenerative diseases. Bioorg Med Chem Lett. 24:204–208. 2014. View Article : Google Scholar : PubMed/NCBI

127 

Putcha P, Danzer KM, Kranich LR, Scott A, Silinski M, Mabbett S, Hicks CD, Veal JM, Steed PM, Hyman BT and McLean PJ: Brain-permeable small-molecule inhibitors of Hsp90 prevent alpha-synuclein oligomer formation and rescue alpha-synuclein-induced toxicity. J Pharmacol Exp Ther. 332:849–857. 2010. View Article : Google Scholar : PubMed/NCBI

128 

Ernst JT, Neubert T, Liu M, Sperry S, Zuccola H, Turnbull A, Fleck B, Kargo W, Woody L, Chiang P, et al: Identification of novel HSP90α/β isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as Huntington's disease. J Med Chem. 57:3382–3400. 2014. View Article : Google Scholar : PubMed/NCBI

129 

Ohkubo S, Kodama Y, Muraoka H, Hitotsumachi H, Yoshimura C, Kitade M, Hashimoto A, Ito K, Gomori A, Takahashi K, et al: TAS-116, a highly selective inhibitor of heat shock protein 90α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models. Mol Cancer Ther. 14:14–22. 2015. View Article : Google Scholar : PubMed/NCBI

130 

Shimomura A, Yamamoto N, Kondo S, Fujiwara Y, Suzuki S, Yanagitani N, Horiike A, Kitazono S, Ohyanagi F, Doi T, et al: First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors. Mol Cancer Ther. 18:531–540. 2019. View Article : Google Scholar : PubMed/NCBI

131 

Doi T, Kurokawa Y, Sawaki A, Komatsu Y, Ozaka M, Takahashi T, Naito Y, Ohkubo S and Nishida T: Efficacy and safety of TAS-116, an oral inhibitor of heat shock protein 90, in patients with metastatic or unresectable gastrointestinal stromal tumour refractory to imatinib, sunitinib and regorafenib: A phase II, single-arm trial. Eur J Cancer. 121:29–39. 2019. View Article : Google Scholar : PubMed/NCBI

132 

Rosser MF and Nicchitta CV: Ligand interactions in the adenosine nucleotide-binding domain of the Hsp90 chaperone, GRP94. I. Evidence for allosteric regulation of ligand binding. J Biol Chem. 275:22798–22805. 2000. View Article : Google Scholar : PubMed/NCBI

133 

Duerfeldt AS, Peterson LB, Maynard JC, Ng CL, Eletto D, Ostrovsky O, Shinogle HE, Moore DS, Argon Y, Nicchitta CV and Blagg BS: Development of a Grp94 inhibitor. J Am Chem Soc. 134:9796–9804. 2012. View Article : Google Scholar : PubMed/NCBI

134 

Patel PD, Yan P, Seidler PM, Patel HJ, Sun W, Yang C, Que NS, Taldone T, Finotti P, Stephani RA, et al: Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2. Nat Chem Biol. 9:677–684. 2013. View Article : Google Scholar : PubMed/NCBI

135 

Crowley VM, Khandelwal A, Mishra S, Stothert AR, Huard DJ, Zhao J, Muth A, Duerfeldt AS, Kizziah JL, Liebermann RL, et al: Development of glucose regulated protein 94-selective inhibitors based on the bnim and radamide scaffold. J Med Chem. 59:3471–3488. 2016. View Article : Google Scholar : PubMed/NCBI

136 

Jiang F, Guo AP, Xu JC, You QD and Xu XL: Discovery of a Potent Grp94 selective inhibitor with anti-inflammatory efficacy in a mouse model of ulcerative colitis. J Med Chem. 61:9513–9533. 2018. View Article : Google Scholar : PubMed/NCBI

137 

Plescia J, Salz W, Xia F, Pennati M, Zaffaroni N, Daidone MG, Meli M, Dohi T, Fortugno P, Nefedova Y, et al: Rational design of shepherdin, a novel anticancer agent. Cancer Cell. 7:457–468. 2005. View Article : Google Scholar : PubMed/NCBI

138 

Altieri DC, Stein GS, Lian JB and Languino LR: TRAP-1, the mitochondrial Hsp90. Biochim Biophys Acta. 1823:767–773. 2012. View Article : Google Scholar : PubMed/NCBI

139 

Lee C, Park HK, Jeong H, Lim J, Lee AJ, Cheon KY, Kim CS, Thomas AP, Bae B, Kim ND, et al: Development of a mitochondria-targeted Hsp90 inhibitor based on the crystal structures of human TRAP1. J Am Chem Soc. 137:4358–4367. 2015. View Article : Google Scholar : PubMed/NCBI

140 

Park HK, Jeong H, Ko E, Lee G, Lee JE, Lee SK, Lee AJ, Im JY, Hu S, Kim SH, et al: Paralog specificity determines subcellular distribution, action mechanism, and anticancer activity of TRAP1 inhibitors. J Med Chem. 60:7569–7578. 2017. View Article : Google Scholar : PubMed/NCBI

141 

Sveen A, Bruun J, Eide PW, Eilertsen IA, Ramirez L, Murumagi A, Arjama M, Danielsen SA, Kryeziu K, Elez E, et al: Colorectal cancer consensus molecular subtypes translated to preclinical models uncover potentially targetable cancer cell dependencies. Clin Cancer Res. 24:794–806. 2018. View Article : Google Scholar : PubMed/NCBI

142 

Piper PW and Millson SH: Mechanisms of resistance to Hsp90 inhibitor drugs: A complex mosaic emerges. Pharmaceuticals (Basel). 4:1400–1422. 2011. View Article : Google Scholar : PubMed/NCBI

143 

Bendell JC, Jones SF, Hart L, Pant S, Moyhuddin A, Lane CM, Earwood C, Murphy P, Patton J, Penley WC, et al: A Phase I Study of the Hsp90 inhibitor AUY922 plus capecitabine for the treatment of patients with advanced solid tumors. Cancer Invest. 33:477–482. 2015. View Article : Google Scholar : PubMed/NCBI

144 

Wang Y, Koay YC and McAlpine SR: How selective are Hsp90 inhibitors for cancer cells over normal cells? Chem Med Chem. 12:353–357. 2017. View Article : Google Scholar : PubMed/NCBI

145 

Mohammadian M, Feizollahzadeh S, Mahmoudi R, Toofani Milani A, Rezapour-Firouzi S and Karimi Douna B: Hsp90 Inhibitor; NVP-AUY922 in combination with doxorubicin induces apoptosis and downregulates VEGF in MCF-7 breast cancer cell line. Asian Pac J Cancer Prev. 21:1773–1778. 2020. View Article : Google Scholar : PubMed/NCBI

146 

Tse AN, Klimstra DS, Gonen M, Shah M, Sheikh T, Sikorski R, Carvajal R, Mui J, Tipian C, O'Reilly E, et al: A phase 1 dose-escalation study of irinotecan in combination with 17-allylamino-17-demethoxygeldanamycin in patients with solid tumors. Clin Cancer Res. 14:6704–6711. 2008. View Article : Google Scholar : PubMed/NCBI

147 

Sulthana S, Banerjee T, Kallu J, Vuppala SR, Heckert B, Naz S, Shelby T, Yambem O and Santra S: Combination therapy of NSCLC using Hsp90 inhibitor and doxorubicin carrying functional nanoceria. Mol Pharm. 14:875–884. 2017. View Article : Google Scholar : PubMed/NCBI

148 

Ono N, Yamazaki T, Tsukaguchi T, Fujii T, Sakata K, Suda A, Tsukuda T, Mio T, Ishii N, Kondoh O and Aoki Y: Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor CH5164840 against non-small-cell lung cancer. Cancer Sci. 104:1346–1352. 2013. View Article : Google Scholar : PubMed/NCBI

149 

Feng Q, Zhang C, Lum D, Druso JE, Blank B, Wilson KF, Welm A, Antonyak MA and Cerione RA: A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis. Nat Commun. 8:144502017. View Article : Google Scholar : PubMed/NCBI

150 

Johnson ML, Yu HA, Hart EM, Weitner BB, Rademaker AW, Patel JD, Kris MG and Riely GJ: Phase I/II study of HSP90 inhibitor AUY922 and erlotinib for EGFR-Mutant lung cancer with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. J Clin Oncol. 33:1666–1673. 2015. View Article : Google Scholar : PubMed/NCBI

151 

Meehan R, Kummar S, Do K, O'Sullivan Coyne G, Juwara L, Zlott J, Rubinstein L, Doroshow JH and Chen AP: A Phase I Study of ganetespib and Ziv-Aflibercept in patients with advanced carcinomas and sarcomas. Oncologist. 23:1269–e1125. 2018. View Article : Google Scholar : PubMed/NCBI

152 

Lee HJ, Shin S, Kang J, Han KC, Kim YH, Bae JW and Park KH: HSP90 Inhibitor, 17-DMAG, alone and in combination with lapatinib attenuates acquired lapatinib-resistance in ER-positive, HER2-overexpressing breast cancer cell line. Cancers (Basel). 12:26302020. View Article : Google Scholar : PubMed/NCBI

153 

Jhaveri K and Modi S: HSP90 inhibitors for cancer therapy and overcoming drug resistance. Adv Pharmacol. 65:471–517. 2012. View Article : Google Scholar : PubMed/NCBI

154 

Chen F, Xie H, Bao H, Violetta L and Zheng S: Combination of HSP90 and autophagy inhibitors promotes hepatocellular carcinoma apoptosis following incomplete thermal ablation. Mol Med Rep. 22:337–343. 2020.PubMed/NCBI

155 

Vaishampayan UN, Burger AM, Sausville EA, Heilbrun LK, Li J, Horiba MN, Egorin MJ, Ivy P, Pacey S and Lorusso PM: Safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of sorafenib and tanespimycin. Clin Cancer Res. 16:3795–3804. 2010. View Article : Google Scholar : PubMed/NCBI

156 

Kawazoe A, Itahashi K, Yamamoto N, Kotani D, Kuboki Y, Taniguchi H, Harano K, Naito Y, Suzuki M, Fukutani M, et al: TAS-116 (Pimitespib), an Oral HSP90 inhibitor, in combination with nivolumab in patients with colorectal cancer and other solid tumors: An open-label, dose-finding, and expansion Phase Ib trial (EPOC1704). Clin Cancer Res. 27:6709–6715. 2021. View Article : Google Scholar : PubMed/NCBI

157 

Roué G, Pérez-Galán P, Mozos A, López-Guerra M, Xargay-Torrent S, Rosich L, Saborit-Villarroya I, Normant E, Campo E and Colomer D: The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78. Blood. 117:1270–1279. 2011. View Article : Google Scholar : PubMed/NCBI

158 

Ishii T, Seike T, Nakashima T, Juliger S, Maharaj L, Soga S, Akinaga S, Cavenagh J, Joel S and Shiotsu Y: Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib. Blood Cancer J. 2:e682012. View Article : Google Scholar : PubMed/NCBI

159 

Mbofung RM, McKenzie JA, Malu S, Zhang M, Peng W, Liu C, Kuiatse I, Tieu T, Williams L, Devi S, et al: HSP90 inhibition enhances cancer immunotherapy by upregulating interferon response genes. Nat Commun. 8:4512017. View Article : Google Scholar : PubMed/NCBI

160 

Proia DA and Kaufmann GF: Targeting heat-shock protein 90 (HSP90) as a complementary strategy to immune checkpoint blockade for cancer therapy. Cancer Immunol Res. 3:583–589. 2015. View Article : Google Scholar : PubMed/NCBI

161 

Rao A, Taylor JL, Chi-Sabins N, Kawabe M, Gooding WE and Storkus WJ: Combination therapy with HSP90 inhibitor 17-DMAG reconditions the tumor microenvironment to improve recruitment of therapeutic T cells. Cancer Res. 72:3196–3206. 2012. View Article : Google Scholar : PubMed/NCBI

162 

Spiegelberg D, Dascalu A, Mortensen AC, Abramenkovs A, Kuku G, Nestor M and Stenerlow B: The novel HSP90 inhibitor AT13387 potentiates radiation effects in squamous cell carcinoma and adenocarcinoma cells. Oncotarget. 6:35652–35666. 2015. View Article : Google Scholar : PubMed/NCBI

163 

Spiegelberg D, Abramenkovs A, Mortensen ACL, Lundsten S, Nestor M and Stenerlow B: The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: An in vitro and in vivo approach. Sci Rep. 10:59232020. View Article : Google Scholar : PubMed/NCBI

164 

Naz S, Banerjee T, Totsingan F, Woody K, Gross RA and Santra S: Therapeutic efficacy of lactonic sophorolipids: Nanoceria-assisted combination therapy of NSCLC using HDAC and Hsp90 inhibitors. Nanotheranostics. 5:391–404. 2021. View Article : Google Scholar : PubMed/NCBI

165 

Lin TY, Guo W, Long Q, Ma A, Liu Q, Zhang H, Huang Y, Chandrasekaran S, Pan C, Lam KS, et al: HSP90 inhibitor encapsulated photo-theranostic nanoparticles for synergistic combination cancer therapy. Theranostics. 6:1324–1335. 2016. View Article : Google Scholar : PubMed/NCBI

166 

Bradbury AR and Marks JD: Antibodies from phage antibody libraries. J Immunol Methods. 290:29–49. 2004. View Article : Google Scholar : PubMed/NCBI

167 

Saw PE and Song EW: Phage display screening of therapeutic peptide for cancer targeting and therapy. Protein Cell. 10:787–807. 2019. View Article : Google Scholar : PubMed/NCBI

168 

Wang J, Masehi-Lano JJ and Chung EJ: Peptide and antibody ligands for renal targeting: Nanomedicine strategies for kidney disease. Biomater Sci. 5:1450–1459. 2017. View Article : Google Scholar : PubMed/NCBI

169 

Fosgerau K and Hoffmann T: Peptide therapeutics: Current status and future directions. Drug Discov Today. 20:122–128. 2015. View Article : Google Scholar : PubMed/NCBI

170 

Petters E, Sokolowska-Wedzina A and Otlewski J: Selection and characterization of single chain antibody fragments specific for Hsp90 as a potential cancer targeting molecule. Int J Mol Sci. 16:19920–19935. 2015. View Article : Google Scholar : PubMed/NCBI

171 

Mochizuki K, Matsukura L, Ito Y, Miyashita N and Taki M: A medium-firm drug-candidate library of cryptand-like structures on T7 phage: Design and selection of a strong binder for Hsp90. Org Biomol Chem. 19:146–150. 2021. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li Z and Luo Y: HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review). Oncol Rep 49: 6, 2023.
APA
Li, Z., & Luo, Y. (2023). HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review). Oncology Reports, 49, 6. https://doi.org/10.3892/or.2022.8443
MLA
Li, Z., Luo, Y."HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)". Oncology Reports 49.1 (2023): 6.
Chicago
Li, Z., Luo, Y."HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)". Oncology Reports 49, no. 1 (2023): 6. https://doi.org/10.3892/or.2022.8443
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z and Luo Y: HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review). Oncol Rep 49: 6, 2023.
APA
Li, Z., & Luo, Y. (2023). HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review). Oncology Reports, 49, 6. https://doi.org/10.3892/or.2022.8443
MLA
Li, Z., Luo, Y."HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)". Oncology Reports 49.1 (2023): 6.
Chicago
Li, Z., Luo, Y."HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)". Oncology Reports 49, no. 1 (2023): 6. https://doi.org/10.3892/or.2022.8443
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