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Unfortunately, peripheral neuropathy (PN) secondary to treatment of MM with PIs has emerged as a clinically relevant complication, which negatively impacts the quality of life of MM survivors. Bortezomib\u2010induced peripheral neuropathy (BIPN) is a dose\u2010limiting toxicity, which develops in 30% to 60% of patients during treatment. Typically, BIPN is a length\u2010dependent sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution. BIPN mechanisms have not yet been fully elucidated. Experimental studies suggest that aggresome formation, endoplasmic reticulum stress, myotoxicity, microtubule stabilization, inflammatory response, and DNA damage could contribute to this neurotoxicity. A new generation of structurally distinct PIs has been developed, being increasingly used in clinical settings. Carfilzomib exhibits a much lower neurotoxicity profile, with a significantly lower incidence of PN compared to BTZ. Pre\u2010existing PN increases the risk of developing BIPN. Besides, BIPN is related to dose, schedule and mode of administration and modifications of these factors have lowered the incidence of PN. However, to date there is no cure for PIs\u2010induced PN (PIIPN), and a careful neurological monitoring and dose adjustment is a key strategy for preserving quality of life. This review critically looks at the pathogenesis, incidence, risk factors, both clinical and pharmacogenetics, clinical phenotype and management of PIIPN. We also make recommendations for further elucidating the whole clinical spectrum of PIIPN.<\/jats:p>","DOI":"10.1111\/jns.12338","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T12:43:23Z","timestamp":1571921003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Bortezomib and other proteosome inhibitors\u2014induced peripheral neurotoxicity: From pathogenesis to treatment"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-9406","authenticated-orcid":false,"given":"Roser","family":"Velasco","sequence":"first","affiliation":[{"name":"Unit of Neuro\u2010Oncology Hospital Universitari de Bellvitge\u2010Institut Catal\u00e0 D'Oncologia L'Hospitalet, IDIBELL  Barcelona Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences Universitat Aut\u00f2noma de Barcelona, and Centro de Investigaci\u00f3n 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6641-288X","authenticated-orcid":false,"given":"Dimitri","family":"Psimaras","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re \u2010 Charles Foix Service de Neurologie Mazarin  Paris France"},{"name":"Inserm U 1127, CNRS UMR 7225 Sorbonne Universit\u00e9s, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM  Paris France"},{"name":"OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments H\u00f4pitaux Universitaires Piti\u00e9\u2010Salpetri\u00e8re\u2010Charles Foix et H\u00f4pital Percy  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas A.","family":"Argyriou","sequence":"additional","affiliation":[{"name":"Department of Neurology \u201cSaint Andrew's\u201d State General Hospital of Patras  Patras 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