{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:45:59Z","timestamp":1787928359870,"version":"build-2784847793"},"reference-count":161,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"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>The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed\/refractory setting. Despite being among the most widely used and highly effective agents for MM, bortezomib can induce adverse events that potentially lead to early discontinuation of the therapy with negative effects on the quality of life and outcome of the patients. Although peripheral neuropathy and myelosuppression have been recognized as the most relevant bortezomib-related adverse effects, cardiac and skeletal muscle toxicities are relatively common in MM treated patients, but they have received much less attention. Here we review the neuromuscular and cardiovascular side effects of bortezomib. focusing on the molecular mechanisms underlying its toxicity. We also discuss our preliminary data on the effects of bortezomib on skeletal muscle tissue in mice receiving the drug.<\/jats:p>","DOI":"10.3390\/cancers12092540","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T09:18:16Z","timestamp":1599470296000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects"],"prefix":"10.3390","volume":"12","author":[{"given":"Elia","family":"Pancheri","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Guglielmi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz M.","family":"Wilczynski","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology Warsaw, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-9232","authenticated-orcid":false,"given":"Manuela","family":"Malatesta","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Anatomy and Histology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Tonin","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Tomelleri","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-9523","authenticated-orcid":false,"given":"Dominika","family":"Nowis","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical University of Warsaw, 02-093 Warsaw, Poland"},{"name":"Laboratory of Experimental Medicine, Medical University of Warsaw, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-8339","authenticated-orcid":false,"given":"Gaetano","family":"Vattemi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple Myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. 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