{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:41:46Z","timestamp":1780566106318,"version":"3.54.1"},"reference-count":90,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Heat-shock proteins (HSPs) are a family of proteins that have received considerable attention over the last several years. They have been classified into six prominent families: high-molecular-mass HSP, 90, 70, 60, 40, and small heat shock proteins. HSPs participate in protein folding, stability, and maturation of several proteins during stress, such as in heat, oxidative stress, fever, and inflammation. Due to the immunogenic host\u2019s role in the combat against cancer cells and the role of the inflammation in the cancer control or progression, abnormal expression of these proteins has been associated with many types of cancer, including esophagogastric cancer. This study aims to review all the evidence concerning the role of HSPs in the pathogenesis and prognosis of esophagogastric cancer and their potential role in future treatment options. This narrative review gathers scientific evidence concerning HSPs in relation to esophagus and gastric cancer. All esophagogastric cancer subtypes are included. The role of HSPs in carcinogenesis, prognostication, and therapy for esophagogastric cancer are discussed. The main topics covered are premalignant conditions for gastric cancer atrophic gastritis, Barrett esophagus, and some viral infections such as human papillomavirus (HPV) and Epstein\u2013Barr virus (EBV). HSPs represent new perspectives on the development, prognostication, and treatment of esophagogastric cancer.<\/jats:p>","DOI":"10.3390\/cells11172664","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:22:56Z","timestamp":1661721776000},"page":"2664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Role of the Heat-Shock Proteins in Esophagogastric Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-0496","authenticated-orcid":false,"given":"Francisco","family":"Tustumi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as Carvalho de Aguiar, 255, S\u00e3o Paulo 05403-000, SP, Brazil"},{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Andrade","family":"Agareno","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Purchio","family":"Galletti","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Benjamim Rosa","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Grams","family":"Quintas","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas de Abreu","family":"Sesconetto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Jos\u00e9","family":"Szor","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Universidade de S\u00e3o Paulo, Av. Dr. En\u00e9as Carvalho de Aguiar, 255, S\u00e3o Paulo 05403-000, SP, Brazil"},{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Wolosker","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, S\u00e3o Paulo 05652-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/BF02172188","article-title":"A new puffing pattern induced by temperature shock and DNP in drosophila","volume":"18","author":"Ritossa","year":"1962","journal-title":"Experientia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-3-319-90725-3_7","article-title":"Heat shock proteins in oxidative and nitrosative stress","volume":"15","author":"Kattaia","year":"2018","journal-title":"Heat Shock Proteins Stress"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12192-012-0320-z","article-title":"Ferruccio Ritossa\u2019s scientific legacy 50 years after his discovery of the heat shock response: A new view of biology, a new society, and a new journal","volume":"17","author":"Santoro","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00018-006-6321-2","article-title":"The small heat shock proteins and their clients","volume":"64","author":"Nakamoto","year":"2007","journal-title":"Experientia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41388-019-1016-y","article-title":"Heat-shock proteins: Chaperoning DNA repair","volume":"39","author":"Dubrez","year":"2020","journal-title":"Oncogene"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zininga, T., Ramatsui, L., and Shonhai, A. (2018). Heat Shock Proteins as Immunomodulants. Molecules, 23.","DOI":"10.3390\/molecules23112846"},{"key":"ref_7","first-page":"212537","article-title":"Correlation between Clinicopathology and Expression of Heat Shock Protein 72 and Glycoprotein 96 in Human Esophageal Squamous Cell Carcinoma","volume":"2010","author":"Wang","year":"2010","journal-title":"Clin. Dev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fgene.2020.00030","article-title":"Varying Architecture of Heat Shock Elements Contributes to Distinct Magnitudes of Target Gene Expression and Diverged Biological Pathways in Heat Stress Response of Bread Wheat","volume":"11","author":"Zhao","year":"2020","journal-title":"Front. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.acr.2021.03.006","article-title":"Targeting heat shock protein 90 for anti-cancer drug development","volume":"Volume 152","author":"Aswad","year":"2021","journal-title":"Advances in Cancer Research"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20407","DOI":"10.1073\/pnas.1209565109","article-title":"Alternative bacterial two-component small heat shock protein systems","volume":"109","author":"Bepperling","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1556\/2060.105.2018.1.4","article-title":"Heat shock proteins and cardiovascular disease","volume":"105","author":"Johnson","year":"2018","journal-title":"Physiol. Int."},{"key":"ref_12","first-page":"1191","article-title":"Identification of a novel autoantibody against heat shock factor 1 in idiopathic inflammatory myopathy","volume":"38","author":"Zhang","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eRB6181","DOI":"10.31744\/einstein_journal\/2022RB6181","article-title":"What is the role of heat shock protein in abdominal organ transplantation?","volume":"20","author":"Calil","year":"2022","journal-title":"Einstein"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/ced.15068","article-title":"Fatigue and expression of heat-shock protein genes in plaque psoriasis","volume":"47","author":"Skoie","year":"2021","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yun, C.W., Kim, H.J., Lim, J.H., and Lee, S.H. (2019). Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in An-ti-Cancer Therapy. Cells, 9.","DOI":"10.3390\/cells9010060"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100995","DOI":"10.1016\/j.tranon.2020.100995","article-title":"Extracellular heat shock proteins and cancer: New perspectives","volume":"14","author":"Albakova","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_17","unstructured":"(2022, July 17). Global Cancer Observatory. Available online: https:\/\/gco.iarc.fr\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1590\/0102-6720201600030003","article-title":"Prognostic factors and sur-vival analysis in esophageal carcinoma","volume":"29","author":"Tustumi","year":"2016","journal-title":"ABCD Arq. Bras. Cir. Dig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1379\/CSC-99r.1","article-title":"Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications","volume":"10","author":"Ciocca","year":"2005","journal-title":"Cell Stress Chaperones"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4020-6401-2_12","article-title":"Heat Shock Protein 90: The Cancer Chaperone","volume":"2","author":"Neckers","year":"2007","journal-title":"Heat Shock Proteins Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0003-4975(02)03641-X","article-title":"Expression of heat shock protein 70 in grossly resected esophageal squamous cell carcinoma","volume":"74","author":"Noguchi","year":"2002","journal-title":"Ann. Thorac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/0300985810375050","article-title":"Canine gastric carcinoma: Immuno-histochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70)","volume":"48","author":"Carrasco","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s10120-013-0279-1","article-title":"Mortalin is a prognostic factor of gastric cancer with normal p53 function","volume":"17","author":"Ando","year":"2014","journal-title":"Gastric Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13643-020-1275-2","article-title":"Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett\u2019s esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: Two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC)","volume":"9","author":"Hamel","year":"2020","journal-title":"Syst. Rev."},{"key":"ref_25","first-page":"2347","article-title":"Expression of heat shock protein 27 in the esophageal tissue of rats with reflux esophagitis","volume":"124","author":"Zheng","year":"2011","journal-title":"Chin. Med. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8961","DOI":"10.1007\/s10661-014-4057-2","article-title":"Assessment of thermal stress adaptation by monitoring Hsp70 and MnSOD in the freshwater gastropod, Bellamya bengalensis (Lamark 1882)","volume":"186","author":"Dutta","year":"2014","journal-title":"Environ. Monit. Assess."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"C931","DOI":"10.1152\/ajpcell.00474.2005","article-title":"Human esophageal microvascular endothelial cells respond to acidic pH stress by PI3K\/AKT and p38 MAPK-regulated induction of Hsp70 and Hsp27","volume":"291","author":"Rafiee","year":"2006","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jtcvs.2009.09.066","article-title":"Heat shock protein 27: Induction by gastroduodenal reflux in vivo and augmentation of human esophageal mucosal cell growth in vitro","volume":"139","author":"Mauchley","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1023\/A:1021601103096","article-title":"On the role of Hsp27 in regulating apoptosis","volume":"8","author":"Concannon","year":"2003","journal-title":"Apoptosis"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shehata, A.M., Saadeldin, I.M., Tukur, H.A., and Habashy, W.S. (2020). Modulation of Heat-Shock Proteins Mediates Chicken Cell Survival against Thermal Stress. Animals, 10.","DOI":"10.3390\/ani10122407"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.7314\/APJCP.2012.13.5.2185","article-title":"Prevalence and pathogenesis of Barrett\u2019s esophagus in Luoyang, China","volume":"13","author":"Zhang","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"St\u00f6gbauer, L., Stummer, W., Senner, V., and Brokinkel, B. (2020). Telomerase activity, TERT expression, hTERT promoter alterations, and alternative lengthening of the telomeres (ALT) in meningiomas\u2014A systematic review. Neurosurg. Rev., 903\u2013910.","DOI":"10.1007\/s10143-019-01087-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3382\/ps.2011-01627","article-title":"Overexpression of heat shock protein 70 and its relationship to intestine under acute heat stress in broilers: 1. Intestinal structure and digestive function","volume":"91","author":"Hao","year":"2012","journal-title":"Poult. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.15403\/jgld.2014.1121.274.tlr","article-title":"TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer","volume":"27","author":"Dargiene","year":"2018","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/j.1745-7254.2007.00589.x","article-title":"Protective effects of heat shock protein70 induced by geranyl- geranylacetone in atrophic gastritis in rats","volume":"28","author":"Liu","year":"2007","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_36","first-page":"164","article-title":"The expression of heat shock protein 70\/90 in patients with atrophic gastritis or gastric cancer and its significance","volume":"12","author":"Sun","year":"2009","journal-title":"Chin. J. Dig."},{"key":"ref_37","first-page":"381","article-title":"Heat Shock Protein 27 Expression is Inversely Correlated with Atrophic Gastritis and Intraepithelial Neoplasia","volume":"58","author":"Nagata","year":"2012","journal-title":"Am. J. Dig. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/nyas.14509","article-title":"Human papillomavirus infection in esophageal squamous cell car-cinoma and esophageal adenocarcinoma: A concise review","volume":"1482","author":"Rajendra","year":"2020","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13027-018-0210-9","article-title":"Prognostic role of HPV infection in esophageal squamous cell carcinoma","volume":"13","author":"Bellyei","year":"2018","journal-title":"Infect. Agents Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12935-016-0283-8","article-title":"Heat shock protein 27 downstream of P38-PI3K\/Akt signaling antag-onizes melatonin-induced apoptosis of SGC-7901 gastric cancer cells","volume":"16","author":"Deng","year":"2016","journal-title":"Cancer Cell Int."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tavakoli, A., Monavari, S.H., Mohammadi, F.S., Kiani, S.J., Armat, S., and Farahmand, M. (2020). Association between Epstein-Barr virus infection and gastric cancer: A systematic review and meta-analysis. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07013-x"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1002\/elps.200800086","article-title":"Epstein-Barr virus upregulates phosphorylated heat shock protein 27 kDa in carcinoma cells using the phosphoinositide 3-kinase\/Akt pathway","volume":"29","author":"Fukagawa","year":"2008","journal-title":"Electrophoresis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tibs.2016.01.003","article-title":"Heat Shock Proteins Promote Cancer: It\u2019s a Protection Racket","volume":"41","author":"Calderwood","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","first-page":"1355","article-title":"SUMOylation of HSP27 regulates PKM2 to promote esophageal squamous cell carcinoma progression","volume":"44","author":"Zhang","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0304-3835(01)00825-4","article-title":"Significant correlation between expression of heat shock proteins 27, 70 and lymphocyte infiltration in esophageal squamous cell carcinoma","volume":"178","author":"Nakajima","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1016\/j.ejca.2004.08.013","article-title":"Expression of heat-shock protein Hsp60 correlated with the apoptotic index and patient prognosis in human oesophageal squamous cell carcinoma","volume":"40","author":"Faried","year":"2004","journal-title":"Eur. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1002\/(SICI)1097-0142(19990415)85:8<1649::AID-CNCR2>3.0.CO;2-V","article-title":"Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus","volume":"85","author":"Kawanishi","year":"1999","journal-title":"Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1067\/msy.2000.105028","article-title":"Clinical application of malignancy potential grading as a prognostic factor of human esophageal cancers","volume":"127","author":"Shiozaki","year":"2000","journal-title":"Surgery"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s12253-017-0342-z","article-title":"Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer","volume":"25","author":"Zoltan","year":"2019","journal-title":"Pathol. Oncol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.3390\/cancers6031382","article-title":"Heat Shock Protein 90 (HSP90) and Her2 in Adenocarcinomas of the Esophagus","volume":"6","author":"Becker","year":"2014","journal-title":"Cancers"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"260","DOI":"10.12998\/wjcc.v7.i3.260","article-title":"Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma","volume":"7","author":"Kauppi","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s00432-002-0357-y","article-title":"Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance","volume":"128","author":"Kapranos","year":"2002","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1159\/000490080","article-title":"HSP70\/HSP90-Organizing Protein Contributes to Gastric Cancer Pro-gression in an Autocrine Fashion and Predicts Poor Survival in Gastric Cancer","volume":"47","author":"Zhai","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"660085","DOI":"10.3389\/fimmu.2021.660085","article-title":"Heat Shock Proteins in Lymphoma Immunotherapy","volume":"12","author":"Albakova","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3389\/fimmu.2016.00171","article-title":"Heat Shock Protein\u2013Peptide and HSP-Based Immunotherapies for the Treatment of Cancer","volume":"7","author":"Shevtsov","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.tips.2016.11.009","article-title":"Heat Shock Proteins and Cancer","volume":"38","author":"Wu","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1111\/cas.14165","article-title":"Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial","volume":"110","author":"Shimizu","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.7150\/jca.18946","article-title":"Phase II Trial of Adjuvant Immunotherapy with Autologous Tumor-derived Gp96 Vaccination in Patients with Gastric Cancer","volume":"8","author":"Zhang","year":"2017","journal-title":"J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41571-021-00594-x","article-title":"Pembrolizumab for HER2+ gastric cancer","volume":"19","author":"Killock","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/modpathol.2011.52","article-title":"Assessment of ErbB2 (Her2) in oesophageal adenocar-cinomas: Summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluo-rescence in situ hybridisation","volume":"24","author":"Langer","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1158\/1078-0432.CCR-11-1000","article-title":"Hsp90 molecular chaperone inhibitors: Are we there yet?","volume":"18","author":"Neckers","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Berezowska, S., Novotny, A., Bauer, K., Feuchtinger, A., Slotta-Huspenina, J., Becker, K., Langer, R., and Walch, A. (2013). Association between HSP90 and Her2 in Gastric and Gastroesophageal Carcinomas. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069098"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1038\/onc.2011.5","article-title":"Heat shock protein Hsp72 plays an essential role in Her2-induced mammary tumorigenesis","volume":"30","author":"Meng","year":"2011","journal-title":"Oncogene"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"35646","DOI":"10.1074\/jbc.M112.377481","article-title":"Heat Shock Factor Hsf1 Cooperates with ErbB2 (Her2\/Neu) Protein to Promote Mammary Tumorigenesis and Metastasis","volume":"287","author":"Xi","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00262-020-02737-y","article-title":"Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepato-cellular carcinoma: A phase I\/II prospective randomized controlled clinical trial","volume":"70","author":"Matsui","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejphar.2018.07.034","article-title":"Molecular targeted therapy: Treating cancer with specificity","volume":"834","author":"Lee","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e358","DOI":"10.1016\/S1470-2045(13)70169-4","article-title":"Inhibition of HSP90 molecular chaperones: Moving into the clinic","volume":"14","author":"Carnero","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Birbo, B., Madu, E.E., Madu, C.O., Jain, A., and Lu, Y. (2021). Role of HSP90 in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910317"},{"key":"ref_70","first-page":"907","article-title":"Hsp90 inhibitor as a sensitizer of cancer cells to different therapies (review)","volume":"46","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.drup.2008.12.002","article-title":"New developments in Hsp90 inhibitors as anti-cancer therapeutics: Mechanisms, clinical perspective and more potential","volume":"12","author":"Li","year":"2009","journal-title":"Drug Resist. Updat."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.3892\/ijo.2014.2575","article-title":"Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor","volume":"45","author":"Vesci","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s10637-019-00889-y","article-title":"A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced esophagogastric cancer","volume":"38","author":"Goyal","year":"2020","journal-title":"Investig. New Drugs"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.bbrc.2014.09.026","article-title":"BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation","volume":"452","author":"Wang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","first-page":"1769","article-title":"Correlation between Tumor-associated Proteins and Response to Neoadjuvant Treatment in Patients with Advanced Squamous-cell Esophageal Cancer","volume":"31","author":"Farkas","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8279","DOI":"10.1158\/1078-0432.CCR-08-0679","article-title":"Protein Expression Profiling in Esophageal Adenocarcinoma Patients Indicates Association of Heat-Shock Protein 27 Expression and Chemotherapy Response","volume":"14","author":"Langer","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(19)30456-5","article-title":"Progress in cancer survival, mortality, and incidence in seven high-income countries 1995\u20132014 (ICBP SUR-VMARK-2): A population-based study","volume":"20","author":"Arnold","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3322\/caac.21601","article-title":"Cancer statistics 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J. Clin."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13073-019-0703-1","article-title":"Molecular profiling for precision cancer therapies","volume":"12","author":"Malone","year":"2020","journal-title":"Genome Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00074","article-title":"Estimated cost of anticancer therapy directed by comprehensive genomic profiling in a single-center study","volume":"2","author":"Chawla","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"532403","DOI":"10.3389\/fonc.2020.532403","article-title":"Molecular Profiling\u2013Based Precision Medicine in Cancer: A Review of Current Evidence and Challenges","volume":"10","author":"Zhang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.trecan.2017.12.004","article-title":"Challenging Standard-of-Care Paradigms in the Precision Oncology Era","volume":"4","author":"Subbiah","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_83","first-page":"1","article-title":"18F-FDG-PET\/CT-measured parameters as potential predictors of residual disease after neoadjuvant chemoradiotherapy in patients with esophageal carcinoma","volume":"1","author":"Tustumi","year":"2022","journal-title":"Radiol. Bras."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Farinha, H.T., Digklia, A., Schizas, D., Demartines, N., Sch\u00e4fer, M., and Mantziari, S. (2022). Immunotherapy for Esophageal Cancer: State-of-the Art in 2021. Cancers, 14.","DOI":"10.3390\/cancers14030554"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Dolcetti, R., de Re, V., and Canzonieri, V. (2018). Immunotherapy for Gastric Cancer: Time for a Personalized Approach?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061602"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.2217\/fon-2020-0189","article-title":"Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E)","volume":"16","author":"Yamamoto","year":"2020","journal-title":"Future Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1158\/1078-0432.CCR-18-2641","article-title":"The Promise of Neoadjuvant Immunotherapy and Surgery for Cancer Treatment","volume":"25","author":"Hoefsmit","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_88","first-page":"79","article-title":"Esophagogastric premalignant conditions. A literature review","volume":"2","author":"Troian","year":"2020","journal-title":"J. Gastric Surg."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Latchford, A., and Jankowski, J.A. (2005). Premalignant Lesions of the Oesophagus: Identification to Management. Upper Gastrointestinal Surgery, Springer.","DOI":"10.1007\/1-84628-066-4_19"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/MD.0000000000005318","article-title":"Human papillomavirus-related esophageal cancer survival: A sys-tematic review and meta-analysis","volume":"95","author":"Guo","year":"2016","journal-title":"Medicine"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:16:22Z","timestamp":1760141782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,27]]},"references-count":90,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11172664"],"URL":"https:\/\/doi.org\/10.3390\/cells11172664","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,27]]}}}