{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:07:53Z","timestamp":1788826073545,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca2+ release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.<\/jats:p>","DOI":"10.3390\/cancers14174126","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:22:56Z","timestamp":1661721776000},"page":"4126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-8215","authenticated-orcid":false,"given":"Elia","family":"Ranzato","sequence":"first","affiliation":[{"name":"DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-5763","authenticated-orcid":false,"given":"Gregorio","family":"Bonsignore","sequence":"additional","affiliation":[{"name":"DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-1810","authenticated-orcid":false,"given":"Simona","family":"Martinotti","sequence":"additional","affiliation":[{"name":"DiSIT-Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11864-008-0067-z","article-title":"Mesothelioma epidemiology, carcinogenesis, and pathogenesis","volume":"9","author":"Yang","year":"2008","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_2","first-page":"478","article-title":"Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children","volume":"56","author":"Fazzo","year":"2020","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cavone, D., Caputi, A., De Maria, L., Cannone, E.S.S., Mansi, F., Birtolo, F., Delfino, M.C., and Vimercati, L. (2019). Epidemiology of Mesothelioma. Environments, 6.","DOI":"10.3390\/environments6070076"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s11912-011-0177-9","article-title":"Malignant pleural mesothelioma","volume":"13","author":"Raja","year":"2011","journal-title":"Curr. Oncol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1053\/j.semtcvs.2009.06.005","article-title":"Pathologic evaluation of malignant pleural mesothelioma","volume":"21","author":"Chirieac","year":"2009","journal-title":"Semin. Thorac. Cardiovasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S311","DOI":"10.21037\/jtd.2017.10.131","article-title":"Target therapy: New drugs or new combinations of drugs in malignant pleural mesothelioma","volume":"10","author":"Zucali","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): A multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrc3701","article-title":"Glucose-regulated proteins in cancer: Molecular mechanisms and therapeutic potential","volume":"14","author":"Lee","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1158\/0008-5472.CAN-07-2950","article-title":"Critical role of the stress chaperone GRP78\/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development","volume":"68","author":"Dong","year":"2008","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1182\/blood-2011-06-357384","article-title":"Inducible knockout of GRP78\/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling","volume":"119","author":"Wey","year":"2012","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29698","DOI":"10.18632\/oncotarget.25679","article-title":"Suppression of stress induction of the 78-kilodalton glucose regulated protein (GRP78) in cancer by IT-139, an anti-tumor ruthenium small molecule inhibitor","volume":"9","author":"Bakewell","year":"2018","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1158\/0008-5472.CAN-07-0325","article-title":"GRP78 induction in cancer: Therapeutic and prognostic implications","volume":"67","author":"Lee","year":"2007","journal-title":"Cancer Res."},{"key":"ref_14","first-page":"13","article-title":"Glucose regulated protein 78: A critical link between tumor microenvironment and cancer hallmarks","volume":"1826","author":"Li","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1042\/BJ20101569","article-title":"Beyond the endoplasmic reticulum: Atypical GRP78 in cell viability, signalling and therapeutic targeting","volume":"434","author":"Ni","year":"2011","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1089\/ars.2009.2485","article-title":"Role of the unfolded protein response regulator GRP78\/BiP in development, cancer, and neurological disorders","volume":"11","author":"Wang","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/onc.2012.130","article-title":"The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies","volume":"32","author":"Luo","year":"2013","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/bjc.2013.66","article-title":"The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma","volume":"108","author":"Dalton","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7082","DOI":"10.1002\/jcp.26631","article-title":"(\u2212)-Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress","volume":"233","author":"Martinotti","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e000154","DOI":"10.1136\/esmoopen-2016-000154","article-title":"Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: A first-in-human, open-label, dose-escalation phase I study with expansion cohort","volume":"1","author":"Burris","year":"2016","journal-title":"ESMO Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.canlet.2017.07.009","article-title":"Sensitivity towards the GRP78 inhibitor KP1339\/IT-139 is characterized by apoptosis induction via caspase 8 upon disruption of ER homeostasis","volume":"404","author":"Mohr","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_22","first-page":"2055","article-title":"Use of recombinant adenovirus to transfer the herpes simplex virus thymidine kinase (HSVtk) gene to thoracic neoplasms: An effective in vitro drug sensitization system","volume":"54","author":"Smythe","year":"1994","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/jcb.22316","article-title":"Spreading of mesothelioma cells is rapamycin-sensitive and requires continuing translation","volume":"108","author":"Ranzato","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jprot.2016.02.021","article-title":"The secretome signature of malignant mesothelioma cell lines","volume":"145","author":"Manfredi","year":"2016","journal-title":"J. Proteom."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ranzato, E., Bonsignore, G., Patrone, M., and Martinotti, S. (2021). Endothelial and Vascular Health: A Tale of Honey, H. Cells, 10.","DOI":"10.3390\/cells10051071"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Volta, V., Ranzato, E., Martinotti, S., Gallo, S., Russo, M.V., Mutti, L., Biffo, S., and Burlando, B. (2013). Preclinical demonstration of synergistic Active Nutrients\/Drug (AND) combination as a potential treatment for malignant pleural mesothelioma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058051"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic assay of cells in vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Belhadj, S., Hermann, N.S., Zhu, Y., Christensen, G., Strasser, T., and Paquet-Durand, F. (2022). Visualizing Cell Death in Live Retina: Using Calpain Activity Detection as a Biomarker for Retinal Degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073892"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e3128","DOI":"10.21769\/BioProtoc.3128","article-title":"Analysis of the Mitochondrial Membrane Potential Using the Cationic JC-1 Dye as a Sensitive Fluorescent Probe","volume":"9","author":"Sivandzade","year":"2019","journal-title":"Bio-Protocol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Martinotti, S., Patrone, M., Balbo, V., Mazzucco, L., and Ranzato, E. (2020). Endothelial response boosted by platelet lysate: The involvement of calcium toolkit. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030808"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/j.bcp.2012.08.022","article-title":"Induction of caspase 8 and reactive oxygen species by ruthenium-derived anticancer compounds with improved water solubility and cytotoxicity","volume":"84","author":"Vidimar","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","first-page":"65","article-title":"Role of calpain in apoptosis","volume":"13","author":"Momeni","year":"2011","journal-title":"Cell J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.jinorgbio.2006.02.013","article-title":"From bench to bedside--preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A)","volume":"100","author":"Hartinger","year":"2006","journal-title":"J. Inorg. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"39872","DOI":"10.1074\/jbc.M406912200","article-title":"Glutathione is required to regulate the formation of native disulfide bonds within proteins entering the secretory pathway","volume":"279","author":"Chakravarthi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1165\/rcmb.2009-0340OC","article-title":"Selective ascorbate toxicity in malignant mesothelioma: A redox Trojan mechanism","volume":"44","author":"Ranzato","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"352794","DOI":"10.1155\/2015\/352794","article-title":"Calcium homeostasis and ER stress in control of autophagy in cancer cells","volume":"2015","author":"Kania","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4161\/cbt.2.2.237","article-title":"Mu-calpain activation in beta-lapachone-mediated apoptosis","volume":"2","author":"Tagliarino","year":"2003","journal-title":"Cancer Biol. Ther."},{"key":"ref_39","first-page":"3649","article-title":"Redox controls UPR to control redox","volume":"127","author":"Eletto","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.bbamcr.2013.01.026","article-title":"Regulation of inositol 1,4,5-trisphosphate receptors during endoplasmic reticulum stress","volume":"1833","author":"Kiviluoto","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1096\/fj.12-218875","article-title":"Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: Involvement of GRP78","volume":"27","author":"Hammadi","year":"2013","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1096\/fj.05-5254fje","article-title":"Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation","volume":"20","author":"Flourakis","year":"2006","journal-title":"FASEB J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.lfs.2019.04.022","article-title":"GRP78: A cell\u2019s response to stress","volume":"226","author":"Ibrahim","year":"2019","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/iub.2502","article-title":"Glucose-regulated protein (GRP78) is an important cell surface receptor for viral invasion, cancers, and neurological disorders","volume":"73","author":"Gopal","year":"2021","journal-title":"IUBMB Life"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1183\/16000617.0063-2016","article-title":"Malignant pleural mesothelioma: An update on investigation, diagnosis and treatment","volume":"25","author":"Bibby","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.annonc.2021.11.005","article-title":"Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"33","author":"Popat","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e2100006","DOI":"10.1002\/smll.202100006","article-title":"Coordination and Redox Dual-Responsive Mesoporous Organosilica Nanoparticles Amplify Immunogenic Cell Death for Cancer Chemoimmunotherapy","volume":"17","author":"Zhang","year":"2021","journal-title":"Small"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bakewell, S., Conde, I., Fallah, Y., McCoy, M., Jin, L., and Shajahan-Haq, A.N. (2020). Inhibition of DNA Repair Pathways and Induction of ROS Are Potential Mechanisms of Action of the Small Molecule Inhibitor BOLD-100 in Breast Cancer. Cancers, 12.","DOI":"10.3390\/cancers12092647"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10637-016-0337-8","article-title":"Molecular mode of action of NKP-1339-a clinically investigated ruthenium-based drug-involves ER- and ROS-related effects in colon carcinoma cell lines","volume":"34","author":"Flocke","year":"2016","journal-title":"Investig. New Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1126\/science.8235595","article-title":"Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria","volume":"262","author":"Rizzuto","year":"1993","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1126\/science.280.5370.1763","article-title":"Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature10230","article-title":"A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter","volume":"476","author":"Raffaello","year":"2011","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1083\/jcb.200205091","article-title":"Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria","volume":"159","author":"Rapizzi","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/sj.onc.1210638","article-title":"Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis","volume":"27","author":"Deniaud","year":"2008","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cell.2004.11.048","article-title":"Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44","volume":"120","author":"Higo","year":"2005","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BC20050031","article-title":"Uncoupled IP3 receptor can function as a Ca2+-leak channel: Cell biological and pathological consequences","volume":"98","author":"Szlufcik","year":"2006","journal-title":"Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/cmdc.201402128","article-title":"Anticancer ruthenium(III) complex KP1019 interferes with ATP-dependent Ca2+ translocation by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)","volume":"9","author":"Sadafi","year":"2014","journal-title":"ChemMedChem"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Xu, D., Yang, H., Yang, Z., Berezowska, S., Gao, Y., Liang, S.Q., Marti, T.M., Hall, S.R.R., Dorn, P., and Kocher, G.J. (2019). Endoplasmic Reticulum Stress Signaling as a Therapeutic Target in Malignant Pleural Mesothelioma. Cancers, 11.","DOI":"10.3390\/cancers11101502"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101047","DOI":"10.1016\/j.redox.2018.11.005","article-title":"Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress","volume":"25","author":"Zhang","year":"2019","journal-title":"Redox Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.3389\/fimmu.2018.03083","article-title":"The C\/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection","volume":"9","author":"Hu","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ge, R., and Kao, C. (2019). Cell Surface GRP78 as a Death Receptor and an Anticancer Drug Target. Cancers, 11.","DOI":"10.3390\/cancers11111787"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/17\/4126\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:15:49Z","timestamp":1760141749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/17\/4126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,26]]},"references-count":62,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cancers14174126"],"URL":"https:\/\/doi.org\/10.3390\/cancers14174126","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,26]]}}}