REFERENCES
1. Gomez CR. Role of heat shock proteins in aging and chronic inflammatory diseases. Geroscience. 2021;43:2515-32.
2. Parma B, Wurdak H, Ceppi P. Harnessing mitochondrial metabolism and drug resistance in non-small cell lung cancer and beyond by blocking heat-shock proteins. Drug Resist Updat. 2022;65:100888.
4. Albakova Z, Mangasarova Y, Albakov A, Gorenkova L. HSP70 and HSP90 in cancer: cytosolic, endoplasmic reticulum and mitochondrial chaperones of tumorigenesis. Front Oncol. 2022;12:829520.
5. Chen Y, Tsai B, Li N, Gao N. Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding. Nat Commun. 2022;13:3410.
6. Krawczyk Z, Gogler-Pigłowska A, Sojka DR, Scieglinska D. The role of heat shock proteins in cisplatin resistance. Anticancer Agents Med Chem. 2018;18:2093-109.
7. Xiong J, Li Y, Tan X, Fu L. Small heat shock proteins in cancers: functions and therapeutic potential for cancer therapy. Int J Mol Sci. 2020;21:6611.
8. Mittal S, Rajala MS. Heat shock proteins as biomarkers of lung cancer. Cancer Biol Ther. 2020;21:477-85.
9. Yun CW, Kim HJ, Lim JH, Lee SH. Heat shock proteins: agents of cancer development and therapeutic targets in anti-cancer therapy. Cells. 2019;9:60.
10. Hu C, Yang J, Qi Z, et al. Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities. MedComm. 2022;3:e161.
11. Huang Y, Li GM. Role of HSP40 proteins in genome maintenance, insulin signaling and cancer therapy. DNA Repair. 2025;149:103839.
12. Vargas-Roig LM, Gago FE, Tello O, Aznar JC, Ciocca DR. Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy. Int J Cancer. 1998;79:468-75.
13. Kaida A, Iwakuma T. Regulation of p53 and cancer signaling by heat shock protein 40/J-domain protein family members. Int J Mol Sci. 2021;22:13527.
14. He K, Zheng X, Zhang L, Yu J. Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax. Mol Cancer Ther. 2013;12:2559-68.
15. Ben Saad A, Bruneau A, Mareux E, et al. Molecular regulation of canalicular ABC transporters. Int J Mol Sci. 2021;22:2113.
16. Zhang M, Huang MN, Dong XD, et al. Overexpression of ABCB1 confers resistance to FLT3 inhibitor FN-1501 in cancer cells: in vitro and in vivo characterization. Am J Cancer Res. 2023;13:6026-37.
17. Abdelhafiz AHA, Serya RAT, Lasheen DS, et al. Molecular design, synthesis and biological evaluation of novel 1,2,5-trisubstituted benzimidazole derivatives as cytotoxic agents endowed with ABCB1 inhibitory action to overcome multidrug resistance in cancer cells. J Enzyme Inhib Med Chem. 2022;37:2710-24.
18. Cui Q, Wang C, Zeng L, Zhou QX, Fan YF. Editorial: Novel small-molecule agents in overcoming multidrug resistance in cancers. Front Chem. 2022;10:921985.
19. Dong XD, Zhang M, Cai CY, et al. Overexpression of ABCB1 associated with the resistance to the KRAS-G12C specific inhibitor ARS-1620 in cancer cells. Front Pharmacol. 2022;13:843829.
20. He CX, Lv Y, Guo M, et al. Complex crystal structure determination of Hsp90N-NVP-AUY922 and in vitro anti-NSCLC activity of NVP-AUY922. Front Oncol. 2022;12:847556.
21. Li L, Wu D, Deng S, et al. NVP-AUY922 alleviates radiation-induced lung injury via inhibition of autophagy-dependent ferroptosis. Cell Death Discov. 2022;8:86.
22. Seggewiss-Bernhardt R, Bargou RC, Goh YT, et al. Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma. Cancer. 2015;121:2185-92.
23. Canonici A, Qadir Z, Conlon NT, et al. The HSP90 inhibitor NVP-AUY922 inhibits growth of HER2 positive and trastuzumab-resistant breast cancer cells. Invest New Drugs. 2018;36:581-9.
24. Lian J, Lin D, Xie X, et al. NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo. Onco Targets Ther. 2017;10:2219-26.
25. Kühnel A, Schilling D, Combs SE, Haller B, Schwab M, Multhoff G. Radiosensitization of HSF-1 knockdown lung cancer cells by low concentrations of Hsp90 inhibitor NVP-AUY922. Cells. 2019;8:1166.
26. Tani T, Tojo N, Ohnishi K. Preferential radiosensitization to glioblastoma cancer stem cell-like cells by a Hsp90 inhibitor, N-vinylpyrrolidone-AUY922. Oncol Lett. 2022;23:102.
27. Yang H, Lee MH, Park I, et al. HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2. Cancer Lett. 2017;411:19-26.
28. Park KS, Yang H, Choi J, et al. The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer. Cancer Lett. 2017;406:47-53.
29. Park KS, Oh B, Lee MH, et al. The HSP90 inhibitor, NVP-AUY922, sensitizes KRAS-mutant non-small cell lung cancer with intrinsic resistance to MEK inhibitor, trametinib. Cancer Lett. 2016;372:75-81.
30. Wendel T, Zhen Y, Suo Z, Bruheim S, Wiedlocha A. The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo. Exp Cell Res. 2016;340:220-6.
31. Mouratidis PXE, Ter Haar G. HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells. Int J Hyperthermia. 2021;38:1443-56.
32. Kitson RRA, Kitsonová D, Siegel D, Ross D, Moody CJ. Geldanamycin, a naturally occurring inhibitor of Hsp90 and a lead compound for medicinal chemistry. J Med Chem. 2024;67:17946-63.
33. Wang K, Ma Q, Ren Y, et al. Geldanamycin destabilizes HER2 tyrosine kinase and suppresses Wnt/beta-catenin signaling in HER2 overexpressing human breast cancer cells. Oncol Rep. 2007;17:89-96.
34. Schulte TW, Blagosklonny MV, Romanova L, et al. Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. Mol Cell Biol. 1996;16:5839-45.
35. Mo Q, Zhang Y, Jin X, et al. Geldanamycin, an inhibitor of Hsp90, increases paclitaxel-mediated toxicity in ovarian cancer cells through sustained activation of the p38/H2AX axis. Tumour Biol. 2016;37:14745-55.
36. Larson N, Roberts S, Ray A, Buckway B, Cheney DL, Ghandehari H.
37. Sun Q, Liu F, Wen Z, et al. Combined effect of heat shock protein inhibitor geldanamycin and free radicals on photodynamic therapy of prostate cancer. J Mater Chem B. 2022;10:1369-77.
38. Fujimoto D, Umemoto S, Mizumoto T, et al. Alvespimycin is identified as a novel therapeutic agent for diabetic kidney disease by chemical screening targeting extracellular vesicles. Sci Rep. 2025;15:14436.
39. Alves R, Santos D, Jorge J, et al. Alvespimycin inhibits heat shock protein 90 and overcomes imatinib resistance in chronic myeloid leukemia cell lines. Molecules. 2023;28:1210.
40. Hu Y, Bobb D, He J, Hill DA, Dome JS. The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biol Ther. 2015;16:949-57.
41. Jhaveri K, Miller K, Rosen L, et al. A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors. Clin Cancer Res. 2012;18:5090-8.
42. Maddocks K, Hertlein E, Chen TL, et al. A phase I trial of the intravenous Hsp90 inhibitor alvespimycin (17-DMAG) in patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Leuk Lymphoma. 2016;57:2212-5.
43. Cui Q, Wen S, Huang P. Targeting cancer cell mitochondria as a therapeutic approach: recent updates. Future Med Chem. 2017;9:929-49.
44. Hayat U, Elliott GT, Olszanski AJ, Altieri DC. Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor. Cancer Biol Ther. 2022;23:117-26.
45. Xiang Y, Liu X, Sun Q, et al. The development of cancers research based on mitochondrial heat shock protein 90. Front Oncol. 2023;13:1296456.
46. Leav I, Plescia J, Goel HL, et al. Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer. Am J Pathol. 2010;176:393-401.
47. Vo VTA, Choi JW, Phan ANH, et al. TRAP1 inhibition increases glutamine synthetase activity in glutamine auxotrophic non-small cell lung cancer cells. Anticancer Res. 2018;38:2187-93.
48. Wang N, Zhu P, Huang R, Sun L, Dong D, Gao Y. Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Exp Ther Med. 2021;22:1246.
49. Wei S, Yin D, Yu S, et al. Antitumor activity of a mitochondrial-targeted HSP90 inhibitor in gliomas. Clin Cancer Res. 2022;28:2180-95.
50. Nguyen TTT, Zhang Y, Shang E, et al. Inhibition of HDAC1/2 along with TRAP1 causes synthetic lethality in glioblastoma model systems. Cells. 2020;9:1661.
51. Maddalena F, Sisinni L, Lettini G, et al. Resistance to paclitxel in breast carcinoma cells requires a quality control of mitochondrial antiapoptotic proteins by TRAP1. Mol Oncol. 2013;7:895-906.
52. Yan C, Oh JS, Yoo SH, et al. The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. Toxicol Appl Pharmacol. 2013;266:9-18.
53. Karpel-Massler G, Ishida CT, Bianchetti E, et al. Inhibition of mitochondrial matrix chaperones and antiapoptotic Bcl-2 family proteins empower antitumor therapeutic responses. Cancer Res. 2017;77:3513-26.
54. Zhang G, Frederick DT, Wu L, et al. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016;126:1834-56.
55. Park HK, Lee JE, Lim J, et al. Combination treatment with doxorubicin and gamitrinib synergistically augments anticancer activity through enhanced activation of Bim. BMC Cancer. 2014;14:431.
56. Patwardhan CA, Kommalapati VK, Llbiyi T, et al. Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin). Sci Rep. 2023;13:13790.
57. Modi S, Stopeck A, Linden H, 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. 2011;17:5132-9.
58. Newman B, Liu Y, Lee HF, Sun D, Wang Y. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells. Cancer Res. 2012;72:4551-61.
59. O’Malley KJ, Langmann G, Ai J, Ramos-Garcia R, Vessella RL, Wang Z. Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance. Prostate. 2012;72:1117-23.
60. Ui T, Morishima K, Saito S, et al. The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous cell carcinoma cell lines via the Akt/XIAP pathway. Oncol Rep. 2014;31:619-24.
61. Schenk E, Hendrickson AE, Northfelt D, et al. Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies. Invest New Drugs. 2013;31:1251-6.
62. Hendrickson AE, Oberg AL, Glaser G, et al. A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma. Gynecol Oncol. 2012;124:210-5.
63. Lee H, Saini N, Howard EW, et al. Ganetespib targets multiple levels of the receptor tyrosine kinase signaling cascade and preferentially inhibits ErbB2-overexpressing breast cancer cells. Sci Rep. 2018;8:6829.
64. Lu Z, Wang Z, Tu Z, Liu H. HSP90 inhibitor Ganetespib enhances the sensitivity of mantle cell lymphoma to Bruton’s tyrosine kinase inhibitor ibrutinib. Front Pharmacol. 2022;13:864194.
65. Chen F, Tang C, Yang F, et al. HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer. Sci Adv. 2024;10:eadk3663.
66. Deycmar S, Mara E, Kerschbaum-Gruber S, Waller V, Georg D, Pruschy M. Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation. Radiat Oncol. 2022;17:72.
67. Saber S, Hasan AM, Mohammed OA, et al. Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: implications from preclinical data for a novel therapeutic approach. Biomed Pharmacother. 2023;164:114918.
68. Subaiea G, Rizvi SMD, Yadav HKS, et al. Ganetespib with methotrexate acts synergistically to impede NF-κB/p65 signaling in human lung cancer A549 cells. Pharmaceuticals. 2023;16:230.
69. Ye M, Huang W, Liu R, et al. Synergistic activity of the HSP90 inhibitor ganetespib with lapatinib reverses acquired lapatinib resistance in HER2-positive breast cancer cells. Front Pharmacol. 2021;12:651516.
70. Alexandrova EM, Xu S, Moll UM. Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner. Cell Death Dis. 2017;8:e2683.
71. Lazenby M, Hills R, Burnett AK, Zabkiewicz J. The HSP90 inhibitor ganetespib: a potential effective agent for Acute Myeloid Leukemia in combination with cytarabine. Leuk Res. 2015;39:617-24.
72. Lombardi R, Sonego M, Pucci B, et al. HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer. Mol Oncol. 2021;15:1005-23.
73. Pillai RN, Fennell DA, Kovcin V, et al. Randomized phase III study of Ganetespib, a heat shock protein 90 inhibitor, with Docetaxel versus Docetaxel in advanced non-small-cell lung cancer (GALAXY-2). J Clin Oncol. 2020;38:613-22.
74. Ramalingam S, Goss G, Rosell R, et al. A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1). Ann Oncol. 2015;26:1741-8.
75. Ikebe E, Shimosaki S, Hasegawa H, et al. TAS-116 (pimitespib), a heat shock protein 90 inhibitor, shows efficacy in preclinical models of adult T-cell leukemia. Cancer Sci. 2022;113:684-96.
76. Ohkubo S, Kodama Y, Muraoka H, 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. 2015;14:14-22.
77. Kawazoe A, Itahashi K, Yamamoto N, 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. 2021;27:6709-15.
78. Lee Y, Sunada S, Hirakawa H, Fujimori A, Nickoloff JA, Okayasu R. TAS-116, a novel Hsp90 inhibitor, selectively enhances radiosensitivity of human cancer cells to X-rays and carbon ion radiation. Mol Cancer Ther. 2017;16:16-24.
79. Suzuki R, Hideshima T, Mimura N, et al. Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with bortezomib in multiple myeloma. Leukemia. 2015;29:510-4.
80. Teranishi R, Takahashi T, Obata Y, et al. Combination of pimitespib (TAS-116) with sunitinib is an effective therapy for imatinib-resistant gastrointestinal stromal tumors. Int J Cancer. 2023;152:2580-93.
81. Doi T, Kurokawa Y, Sawaki A, et al. 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. 2019;121:29-39.
82. Shimomura A, Yamamoto N, Kondo S, et al. First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors. Mol Cancer Ther. 2019;18:531-40.
83. Kurokawa Y, Honma Y, Sawaki A, et al. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2022;33:959-67.
85. Nan C, Zheng Y, Fan H, Sun H, Huang S, Li N. Antitumorigenic effect of Hsp90 inhibitor SNX-2112 on tongue squamous cell carcinoma is enhanced by low-intensity ultrasound. Onco Targets Ther. 2020;13:7907-19.
86. Zhao D, Xu YM, Cao LQ, et al. Complex crystal structure determination and in vitro anti-non-small cell lung cancer activity of Hsp90N inhibitor SNX-2112. Front Cell Dev Biol. 2021;9:650106.
87. Cheng X, Qin L, Deng L, et al. SNX-2112 induces apoptosis and inhibits proliferation, invasion, and migration of non-small cell lung cancer by downregulating epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. J Cancer. 2021;12:5825-37.
88. Wang R, Shao F, Liu Z, et al. The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-κB and disruption of mitochondria-dependent pathways. Chem Biol Interact. 2013;205:1-10.
89. Liu Y, Wang X, Wang Y, et al. Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells. Int J Oncol. 2015;46:299-307.
90. Infante JR, Weiss GJ, Jones S, et al. Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours. Eur J Cancer. 2014;50:2897-904.
91. Wang X, Wang S, Liu Y, et al. Comparative effects of SNX-7081 and SNX-2112 on cell cycle, apoptosis and Hsp90 client proteins in human cancer cells. Oncol Rep. 2015;33:230-8.
92. Kaufman KL, Jenkins Y, Alomari M, et al. The Hsp90 inhibitor SNX-7081 is synergistic with fludarabine nucleoside via DNA damage and repair mechanisms in human, p53-negative chronic lymphocytic leukemia. Oncotarget. 2015;6:40981-97.
93. Sharma S, Joshi S, Kalidindi T, et al. Unraveling the mechanism of epichaperome modulation by Zelavespib: biochemical insights on target occupancy and extended residence time at the site of action. Biomedicines. 2023;11:2599.
94. Saber S, Abdelhady R, Elhemely MA, et al. PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond. Front Pharmacol. 2024;15:1475998.
95. Kale Ş, Korcum AF, Dündar E, Erin N. HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:253-62.
96. Speranza G, Anderson L, Chen AP, et al. First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile. Invest New Drugs. 2018;36:230-9.
97. Asdemir A, Özgür A. Molecular mechanism of anticancer effect of heat shock protein 90 inhibitor BIIB021 in human bladder cancer cell line. Naunyn Schmiedebergs Arch Pharmacol. 2024;397:5167-77.
98. He W, Ye X, Huang X, et al. Hsp90 inhibitor, BIIB021, induces apoptosis and autophagy by regulating mTOR-Ulk1 pathway in imatinib-sensitive and -resistant chronic myeloid leukemia cells. Int J Oncol. 2016;48:1710-20.
99. Dickson MA, Okuno SH, Keohan ML, et al. Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors. Ann Oncol. 2013;24:252-7.
100. Wang XT, Bao CH, Jia YB, et al. BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation. Biochem Biophys Res Commun. 2014;452:945-50.
101. Woodhead AJ, Angove H, Carr MG, et al. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J Med Chem. 2010;53:5956-69.
102. Williams NO, Quiroga D, Johnson C, et al. Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer. Ther Adv Med Oncol. 2023;15:17588359231217976.
103. Spiegelberg D, Abramenkovs A, Mortensen ACL, Lundsten S, Nestor M, Stenerlöw B. The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach. Sci Rep. 2020;10:5923.
104. Naz S, Leiker AJ, Choudhuri R, et al. Pharmacological inhibition of HSP90 radiosensitizes head and neck squamous cell carcinoma xenograft by inhibition of DNA damage repair, nucleotide metabolism, and radiation-induced tumor vasculogenesis. Int J Radiat Oncol Biol Phys. 2021;110:1295-305.
105. Lundsten S, Spiegelberg D, Raval NR, Nestor M. The radiosensitizer Onalespib increases complete remission in (177)Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts. Eur J Nucl Med Mol Imaging. 2020;47:980-90.
106. Slovin S, Hussain S, Saad F, et al. Pharmacodynamic and clinical results from a phase I/II study of the HSP90 inhibitor Onalespib in combination with Abiraterone acetate in prostate cancer. Clin Cancer Res. 2019;25:4624-33.
107. Canella A, Welker AM, Yoo JY, et al. Efficacy of Onalespib, a long-acting second-generation HSP90 inhibitor, as a single agent and in combination with Temozolomide against malignant gliomas. Clin Cancer Res. 2017;23:6215-26.
108. Courtin A, Smyth T, Hearn K, et al. Emergence of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer can be delayed by an upfront combination with the HSP90 inhibitor onalespib. Br J Cancer. 2016;115:1069-77.
109. Wagner AJ, Agulnik M, Heinrich MC, et al. Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour. Eur J Cancer. 2016;61:94-101.
110. Ewers KM, Patil S, Kopp W, et al. HSP90 inhibition synergizes with cisplatin to eliminate basal-like pancreatic ductal adenocarcinoma cells. Cancers. 2021;13:6163.
111. Gökşen Tosun N, Kaplan Ö. Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263. Breast Cancer Res Treat. 2025;210:493-506.
112. Riess JW, Reckamp KL, Frankel P, et al. Erlotinib and Onalespib lactate focused on EGFR exon 20 insertion non-small cell lung cancer (NSCLC): a California Cancer Consortium phase I/II trial (NCI 9878). Clin Lung Cancer. 2021;22:541-8.
113. Konstantinopoulos PA, Cheng SC, Supko JG, et al. Combined PARP and HSP90 inhibition: preclinical and Phase 1 evaluation in patients with advanced solid tumours. Br J Cancer. 2022;126:1027-36.
114. Kaplan Ö, Gökşen Tosun N. Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line. Med Oncol. 2024;41:194.
115. Paraiso KH, Haarberg HE, Wood E, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012;18:2502-14.
116. Sun C, Bai M, Ke W, Wang X, Zhao X, Lu Z. The HSP90 inhibitor, XL888, enhanced cell apoptosis via downregulating STAT3 after insufficient radiofrequency ablation in hepatocellular carcinoma. Life Sci. 2021;282:119762.
117. Kaplan Ö. Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888. Med Oncol. 2023;40:318.
118. Eroglu Z, Chen YA, Gibney GT, et al. Combined BRAF and HSP90 inhibition in patients with unresectable BRAF (V600E)-mutant melanoma. Clin Cancer Res. 2018;24:5516-24.
119. Eroglu Z, Chen YA, Smalley I, et al. Combined BRAF, MEK, and heat-shock protein 90 inhibition in advanced BRAF V600-mutant melanoma. Cancer. 2024;130:232-43.
120. Mshaik R, Simonet J, Georgievski A, et al. HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias. Blood Cancer J. 2021;11:61.
121. Massey AJ, Schoepfer J, Brough PA, et al. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol Cancer Ther. 2010;9:906-19.
122. Stingl L, Stühmer T, Chatterjee M, Jensen MR, Flentje M, Djuzenova CS. Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction. Br J Cancer. 2010;102:1578-91.
123. Bao R, Lai CJ, Qu H, et al. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res. 2009;15:4046-57.
124. Bao R, Lai CJ, Wang DG, et al. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol Cancer Ther. 2009;8:3296-306.
125. Li HJ, Wang QS, Han W, et al. Anti-NSCLC activity in vitro of Hsp90N inhibitor KW-2478 and complex crystal structure determination of Hsp90N-KW-2478. J Struct Biol. 2021;213:107710.
126. Nakashima T, Ishii T, Tagaya H, et al. 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. 2010;16:2792-802.
127. Ishii T, Seike T, Nakashima T, et al. Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib. Blood Cancer J. 2012;2:e68.
128. Wang J, An J, Tian L, et al. KW2478 and cisplatin synergistically anti-colorectal cancer by targeting PI3K/AKT/mTOR pathway. Anticancer Agents Med Chem. 2025;25:800-10.
129. Cavenagh J, Oakervee H, Baetiong-Caguioa P, 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. 2017;117:1295-302.
130. Vermeulen K, Naus E, Ahamed M, et al. Evaluation of [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90. Theranostics. 2019;9:554-72.
131. Brasca MG, Mantegani S, Amboldi N, et al. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem. 2013;21:7047-63.
132. Barbagallo I, Parenti R, Zappalà A, et al. Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma. Acta Histochem. 2015;117:705-11.
133. Fogliatto G, Gianellini L, Brasca MG, et al. NMS-E973, a novel synthetic inhibitor of Hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. Clin Cancer Res. 2013;19:3520-32.
134. Yang X, Tohda C. Heat shock cognate 70 inhibitor, VER-155008, reduces memory deficits and axonal degeneration in a mouse model of Alzheimer’s disease. Front Pharmacol. 2018;9:48.
135. Sakai K, Inoue M, Mikami S, et al. Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism. Thorac Cancer. 2021;12:491-503.
136. Pham PH, Sokeechand BSH, Hamilton ME, et al. VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses. Antiviral Res. 2019;162:151-62.
137. Huang L, Wang Y, Bai J, et al. Blockade of HSP70 by VER-155008 synergistically enhances bortezomib-induced cytotoxicity in multiple myeloma. Cell Stress Chaperones. 2020;25:357-67.
138. Wu E, Wu C, Jia K, Zhou S, Sun L. HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis. Mol Biol Cell. 2024;35:ar108.
139. Wu L, Feng J, Lin H, Chen P. KNK437 suppresses the growth of non-small cell lung cancer cells by targeting heat shock factor 1. Drug Dev Res. 2025;86:e70141.
140. Oommen D, Prise KM. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways. Biochem Biophys Res Commun. 2012;421:538-43.
141. Taba K, Kuramitsu Y, Ryozawa S, et al. KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. Chemotherapy. 2011;57:12-6.
142. Yang LY, Greig NH, Tweedie D, et al. The p53 inactivators pifithrin-μ and pifithrin-α mitigate TBI-induced neuronal damage through regulation of oxidative stress, neuroinflammation, autophagy and mitophagy. Exp Neurol. 2020;324:113135.
143. Sekihara K, Harashima N, Tongu M, et al. Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells. PLoS One. 2013;8:e78772.
144. Kaiser M, Kühnl A, Reins J, et al. Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia. Blood Cancer J. 2011;1:e28.
145. Lv J, Wang Y, Lv J, et al. Pifithrin-μ sensitizes mTOR-activated liver cancer to sorafenib treatment. Cell Death Dis. 2025;16:42.
146. Koren J 3rd, Miyata Y, Kiray J, et al. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance. PLoS One. 2012;7:e35566.
147. Wang AM, Miyata Y, Klinedinst S, et al. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013;9:112-8.
148. Chandra V, Garland J, Rai R, et al. Mortalin and PINK1/parkin-mediated mitophagy represent ovarian cancer-selective targets for drug development. Adv Sci. 2025;12:e05592.
149. Garland J, Hussain S, Rai R, Kennedy AL, Isingizwe ZR, Benbrook DM. Targeting HSP70-E7 interaction with SHetA2: a novel therapeutic strategy for cervical cancer. J Med Virol. 2024;96:e70088.
150. Dechbumroong P, Hu R, Keaswejjareansuk W, Namdee K, Liang XJ. Recent advanced lipid-based nanomedicines for overcoming cancer resistance. Cancer Drug Resist. 2024;7:24.
151. Summey R, Uyar D. Ovarian cancer resistance to PARPi and platinum-containing chemotherapy. Cancer Drug Resist. 2022;5:637-46.
152. Gupta G, Merhej G, Saravanan S, Chen H. Cancer resistance to immunotherapy: what is the role of cancer stem cells? Cancer Drug Resist. 2022;5:981-94.
153. Singh MK, Shin Y, Ju S, et al. Heat shock response and heat shock proteins: current understanding and future opportunities in human diseases. Int J Mol Sci. 2024;25:4209.
154. Alimardan Z, Abbasi M, Hasanzadeh F, Aghaei M, Khodarahmi G, Kashfi K. Heat shock proteins and cancer: the FoxM1 connection. Biochem Pharmacol. 2023;211:115505.
155. Rastogi S, Joshi A, Sato N, et al. An update on the status of HSP90 inhibitors in cancer clinical trials. Cell Stress Chaperones. 2024;29:519-39.
156. Scott JS, Michaelides IN, Schade M. Property-based optimisation of PROTACs. RSC Med Chem. ;2024:449-56.
