{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:16:29Z","timestamp":1789514189993,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"POR Calabria FESR \u2013 FSE 2014-2020 Action 1.2.2","award":["NANOCAL-CUP J28C17000200006"],"award-info":[{"award-number":["NANOCAL-CUP J28C17000200006"]}]},{"name":"European Union and MIUR, European Social Fund-PON R&amp;I 2014-2020","award":["PhD Fellowship code:DOT1305904-1; CUP H26J17000030006"],"award-info":[{"award-number":["PhD Fellowship code:DOT1305904-1; CUP H26J17000030006"]}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 15738\/2014"],"award-info":[{"award-number":["IG 15738\/2014"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR\u2212) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to assess cells metabolic response to MSNs treatments. FOL-MSN-BTZ exclusively killed FR+ MM cells, leading to an apoptotic rate that was comparable to that induced by free BTZ, and the effect was accompanied by metabolic dysfunction and oxidative stress. Importantly, FOL-MSN-BTZ treated FR\u2212 normal cells did not show any significant sign of injury or metabolic perturbation, while free BTZ was still highly toxic. Notably, the vehicle alone (MSN-FOL) did not affect any biological process in both tested cell models. These data show the striking specificity of FOL-MSN-BTZ toward FR+ tumor cells and the outstanding safety of the MSN-FOL vehicle, paving the way for a future exploitation of FOL-MSN-BTZ in MM target therapy.<\/jats:p>","DOI":"10.3390\/cancers12092709","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T21:01:21Z","timestamp":1600722081000},"page":"2709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Alessandra","family":"Nigro","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-8454","authenticated-orcid":false,"given":"Luca","family":"Frattaruolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosa","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"De Napoli","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Comand\u00e8","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"De Santo","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Perrotta","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, Centre for Microscopy and Microanalysis (CM2), Transmission Electron Microscopy Laboratory, University of Calabria, Rende, 87036 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-6232","authenticated-orcid":false,"given":"Antonella","family":"Leggio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Pasqua","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-1541","authenticated-orcid":false,"given":"Diego","family":"Sisci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Cappello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-0805","authenticated-orcid":false,"given":"Catia","family":"Morelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1177\/107327480301000502","article-title":"Bortezomib (PS-341): A novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers","volume":"10","author":"Richardson","year":"2003","journal-title":"Cancer Control"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1038\/srep05896","article-title":"Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition","volume":"4","author":"Maharjan","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/sj.leu.2404528","article-title":"Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma","volume":"21","author":"Bonvini","year":"2007","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2147\/tcrm.2006.2.3.271","article-title":"Bortezomib (Velcade\u2122) in the treatment of multiple myeloma","volume":"2","author":"Morgan","year":"2006","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3390\/toxics3030294","article-title":"An overview of bortezomib-induced neurotoxicity","volume":"3","author":"Meregalli","year":"2015","journal-title":"Toxics"},{"key":"ref_7","first-page":"1","article-title":"Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles","volume":"4","author":"Singh","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.biopha.2018.10.167","article-title":"Mesoporous silica nanoparticles for therapeutic\/diagnostic applications","volume":"109","author":"Jafari","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1039\/c1nr10253b","article-title":"PEG-templated mesoporous silica nanoparticles exclusively target cancer cells","volume":"3","author":"Morelli","year":"2011","journal-title":"Nanoscale"},{"key":"ref_10","unstructured":"Health, U.D.O., and Services, H. (2019). Food and Drug Administration CFR\u2014Code of Federal Regulations Title 21."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nigro, A., Pellegrino, M., Greco, M., Comand\u00e8, A., Sisci, D., Pasqua, L., Leggio, A., and Morelli, C. (2018). Dealing with skin and blood-brain barriers: The unconventional challenges of mesoporous silica nanoparticles. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040250"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2174\/1389557516666160321113620","article-title":"Mesoporous Silica Nanoparticles in Cancer Therapy: Relevance of the Targeting Function","volume":"16","author":"Pasqua","year":"2016","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Croissant, J.G., Fatieiev, Y., and Khashab, N.M. (2017). Degradability and Clearance of Silicon, Organosilica, Silsesquioxane, Silica Mixed Oxide, and Mesoporous Silica Nanoparticles. Adv. Mater., 29.","DOI":"10.1002\/adma.201604634"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Croissant, J.G., Fatieiev, Y., Almalik, A., and Khashab, N.M. (2018). Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications. Adv. Healthc. Mater., 7.","DOI":"10.1002\/adhm.201700831"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Narayan, R., Nayak, U.Y., Raichur, A.M., and Garg, S. (2018). Mesoporous silica nanoparticles: A comprehensive review on synthesis and recent advances. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030118"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.apsb.2018.01.007","article-title":"Mesoporous silica nanoparticles for drug and gene delivery","volume":"8","author":"Zhou","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1515","DOI":"10.1002\/wnan.1515","article-title":"Functional mesoporous silica nanoparticles for bio-imaging applications","volume":"11","author":"Cha","year":"2019","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1039\/C4SC03549F","article-title":"Mesoporous silica nanoparticles for 19 F magnetic resonance imaging, fluorescence imaging, and drug delivery","volume":"6","author":"Nakamura","year":"2015","journal-title":"Chem. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.ajps.2018.01.006","article-title":"Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery","volume":"13","author":"Slita","year":"2018","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_20","unstructured":"Pasqua, L., Leggio, A., Liguori, A., Morelli, C., and And\u00f2, S. (2020, September 21). EP3288955 (B1)-Bortezomib-Based Delivery System. Available online: https:\/\/patents.google.com\/patent\/WO2016174693A1\/nl."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Burns, J.S., and Manda, G. (2017). Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122755"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1080\/10428194.2018.1453066","article-title":"Expression of functional folate receptors in multiple myeloma","volume":"59","author":"Zhou","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151596","DOI":"10.1016\/j.anndiagpath.2020.151596","article-title":"Correlation of folate receptor alpha expression with clinicopathological parameters and outcome in triple negative breast cancer","volume":"48","author":"Zagorac","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.drup.2014.10.002","article-title":"The folate receptor as a rational therapeutic target for personalized cancer treatment","volume":"17","author":"Assaraf","year":"2014","journal-title":"Drug Resist. Updates"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0169-409X(02)00042-X","article-title":"Folate-mediated delivery of macromolecular anticancer therapeutic agents","volume":"54","author":"Lu","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.addr.2004.01.001","article-title":"Distribution, functionality and gene regulation of folate receptor isoforms: Implications in targeted therapy","volume":"56","author":"Elnakat","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4110\/in.2016.16.6.337","article-title":"Folate Receptor-Targeted Diagnostics and Therapeutics for Inflammatory Diseases","volume":"16","author":"Yi","year":"2016","journal-title":"Immune Netw."},{"key":"ref_28","first-page":"655","article-title":"Mesoporous silica nanoparticles as a carrier platform for intracellular delivery of nucleic acids","volume":"82","author":"Keasberry","year":"2017","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cha, W., Fan, R., Miao, Y., Zhou, Y., Qin, C., Shan, X., Wan, X., and Li, J. (2017). Mesoporous silica nanoparticles as carriers for intracellular delivery of nucleic acids and subsequent therapeutic applications. Molecules, 22.","DOI":"10.3390\/molecules22050782"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sun, X., Wang, N., Yang, L.-Y., Ouyang, X.-K., and Huang, F. (2019). Folic acid and PEI modified mesoporous silica for targeted delivery of curcumin. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11090430"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Abdal Dayem, A., Hossain, M.K., Lee, S.B., Kim, K., Saha, S.K., Yang, G.-M., Choi, H.Y., and Cho, S.-G. (2017). The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010120"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1016\/j.biopha.2018.11.093","article-title":"Cardiac and pulmonary toxicity of mesoporous silica nanoparticles is associated with excessive ROS production and redox imbalance in Wistar rats","volume":"109","author":"Hozayen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1007\/s11356-018-3695-2","article-title":"The size-dependent genotoxicity and oxidative stress of silica nanoparticles on endothelial cells","volume":"26","author":"Zhou","year":"2019","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12171","DOI":"10.1021\/acsnano.9b06706","article-title":"Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery","volume":"13","author":"Villalonga","year":"2019","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13164","DOI":"10.1039\/C9CC07250K","article-title":"Stimulus-responsive nanomotors based on gated enzyme-powered Janus Au\u2013mesoporous silica nanoparticles for enhanced cargo delivery","volume":"55","author":"Villalonga","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14700","DOI":"10.18632\/oncotarget.3739","article-title":"Assessment of folate receptor-\u03b2 expression in human neoplastic tissues","volume":"6","author":"Shen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1126\/science.281.5381.1312","article-title":"Caspases: Enemies within","volume":"281","author":"Thornberry","year":"1998","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14374","DOI":"10.1073\/pnas.202445099","article-title":"Molecular sequelae of proteasome inhibition in human multiple myeloma cells","volume":"99","author":"Mitsiades","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1111\/bph.12416","article-title":"Parthanatos: Mitochondrial-linked mechanisms and therapeutic opportunities","volume":"171","author":"Fatokun","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1038\/cdd.2012.90","article-title":"TRAIL induces necroptosis involving RIPK1\/RIPK3-dependent PARP-1 activation","volume":"19","author":"Arshad","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24980","DOI":"10.18632\/oncotarget.25166","article-title":"Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells","volume":"9","author":"Vangapandu","year":"2018","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.bpj.2015.08.002","article-title":"Mitoenergetic Dysfunction Triggers a Rapid Compensatory Increase in Steady-State Glucose Flux","volume":"109","author":"Schirris","year":"2015","journal-title":"Biophys. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/cpt.545","article-title":"Role of Passive Diffusion, Transporters, and Membrane Trafficking-Mediated Processes in Cellular Drug Transport","volume":"101","author":"Cocucci","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1900860","DOI":"10.1002\/advs.201900860","article-title":"PINK1-Dependent Mitophagy Regulates the Migration and Homing of Multiple Myeloma Cells via the MOB1B-Mediated Hippo-YAP\/TAZ Pathway","volume":"7","author":"Fan","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1158\/1078-0432.CCR-14-1088","article-title":"Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin","volume":"21","author":"Bajpai","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2174\/1568009618666181003170027","article-title":"The Association of Neuronal Stress with Activating Transcription Factor 3 in Dorsal Root Ganglion of in vivo and in vitro Models of Bortezomib- Induced Neuropathy","volume":"19","author":"Yin","year":"2019","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tibullo, D., Giallongo, C., Romano, A., Vicario, N., Barbato, A., Puglisi, F., Parenti, R., Amorini, A.M., Wissam Saab, M., and Tavazzi, B. (2020). Mitochondrial Functions, Energy Metabolism and Protein Glycosylation are Interconnected Processes Mediating Resistance to Bortezomib in Multiple Myeloma Cells. Biomolecules, 10.","DOI":"10.3390\/biom10050696"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.bbamem.2016.06.023","article-title":"Interactions between silica nanoparticles and phospholipid membranes","volume":"1858","author":"Kettiger","year":"2016","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_49","first-page":"4147","article-title":"Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: Effects of size and surface charge groups","volume":"7","author":"Ekkapongpisit","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1096\/fj.12-215798","article-title":"Mitochondria-localized caveolin in adaptation to cellular stress and injury","volume":"26","author":"Fridolfsson","year":"2012","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1096\/fj.14-252320","article-title":"Regulation of intracellular signaling and function by caveolin","volume":"28","author":"Fridolfsson","year":"2014","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/j.pain.0000000000001540","article-title":"Chemotherapy-induced peripheral neuropathy: Where are we now?","volume":"160","author":"Colvin","year":"2019","journal-title":"Pain"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ludman, T., and Melemedjian, O.K. (2019). Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy. Mol. Pain, 15.","DOI":"10.1177\/1744806919837429"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.phrs.2016.01.029","article-title":"Oxidative stress and proteasome inhibitors in multiple myeloma","volume":"105","author":"Lipchick","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Guang, M.H.Z., Kavanagh, E.L., Dunne, L.P., Dowling, P., Zhang, L., Lindsay, S., Bazou, D., Goh, C.Y., Hanley, C., and Bianchi, G. (2019). Targeting Proteotoxic Stress in Cancer: A Review of the Role that Protein Quality Control Pathways Play in Oncogenesis. Cancers, 11.","DOI":"10.3390\/cancers11010066"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"El Arfani, C., De Veirman, K., Maes, K., De Bruyne, E., and Menu, E. (2018). Metabolic Features of Multiple Myeloma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041200"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13045-018-0575-7","article-title":"Inhibition of thioredoxin activates mitophagy and overcomes adaptive bortezomib resistance in multiple myeloma","volume":"11","author":"Zheng","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3389\/fonc.2018.00126","article-title":"Signaling Pathways Regulating Redox Balance in Cancer Metabolism","volume":"8","author":"Porporato","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3389\/fonc.2018.00333","article-title":"Metabolic Plasticity of Tumor Cell Mitochondria","volume":"8","author":"Cannino","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1111\/bph.14063","article-title":"Characterization of a rat model of bortezomib-induced painful neuropathy","volume":"174","author":"Duggett","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1084\/jem.20170584","article-title":"Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain","volume":"215","author":"Stockstill","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1158\/1078-0432.CCR-15-3163","article-title":"A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma","volume":"22","author":"Magrangeas","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1158\/1078-0432.CCR-16-0625","article-title":"Progress and Paradigms in Multiple Myeloma","volume":"22","author":"Anderson","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s40268-019-0269-9","article-title":"Bortezomib for the Treatment of Hematologic Malignancies: 15 Years Later","volume":"19","author":"Robak","year":"2019","journal-title":"Drugs R D"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Pellegrino, M., Rizza, P., Dona, A., Nigro, A., Ricci, E., Fiorillo, M., Perrotta, I., Lanzino, M., Giordano, C., and Bonofiglio, D. (2019). FoxO3a as a Positive Prognostic Marker and a Therapeutic Target in Tamoxifen-Resistant Breast Cancer. Cancers, 11.","DOI":"10.3390\/cancers11121858"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Frattaruolo, L., Fiorillo, M., Brindisi, M., Curcio, R., Dolce, V., Lacret, R., Truman, A.W., Sotgia, F., Lisanti, M.P., and Cappello, A.R. (2019). Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress. Cells, 8.","DOI":"10.3390\/cells8111408"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Armentano, B., Curcio, R., Brindisi, M., Mancuso, R., Rago, V., Ziccarelli, I., Frattaruolo, L., Fiorillo, M., Dolce, V., and Gabriele, B. (2020). 5-(Carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ros levels and mitochondrial dysfunction in breast and cervical cancer. Biomedicines, 8.","DOI":"10.3390\/biomedicines8020035"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/leu.2017.329","article-title":"Management of relapsed and refractory multiple myeloma: Novel agents, antibodies, immunotherapies and beyond","volume":"32","author":"Chim","year":"2018","journal-title":"Leukemia"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sarin, V., Yu, K., Ferguson, I.D., Gugliemini, O., Nix, M.A., Hann, B., Sirota, M., and Wiita, A.P. (2020). Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis. Leukemia.","DOI":"10.1101\/847368"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/9\/2709\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:13Z","timestamp":1760177533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/9\/2709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,21]]},"references-count":69,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["cancers12092709"],"URL":"https:\/\/doi.org\/10.3390\/cancers12092709","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,21]]}}}