title: Neurotoxicity induced by antineoplastic proteasome inhibitors.
abstract: In the last ten years, the proteasome has become one of the most attractive targets for the treatment of several cancer malignancies. Like other types of antineoplastic agents, proteasome inhibitors cause toxic peripheral neuropathy, which indeed is one of the limiting side effects of these treatments, and which thus curtails its potential effectiveness. Bortezomib was the first proteasome inhibitor approved for clinical use and is currently the first line treatment for multiple myeloma. The incidence of neuropathy induced by bortezomib is around 30-60%. Although the neurotoxic mechanisms are not completely understood, experimental studies suggest that aggresome formation, endoplasmic reticulum stress, mitotoxicity, inflammatory response, and DNA damage could contribute to this neurotoxicity. Additionally, the second generation of proteasome inhibitors, headed by carfilzomib, is currently being developed in order to reduce the toxic profile, with promising results. However, more extensive clinical experience and further experimental research are needed in order to determine the potential benefits of the second generation over bortezomib. The present review summarizes the main clinical features and mechanistic events related to the neuropathy induced by proteasome-inhibitors.
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors: Albert
authors: A
authors: Alé
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors: Jordi
authors: J
authors: Bruna
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors: Xavier
authors: X
authors: Navarro
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: esther.udina@uab.cat.
authors: Esther
authors: E
authors: Udina
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D061988:Proteasome Inhibitors / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors
keywords: Bortezomib; Carfilzomib; Neurotoxicity; Peripheral neurophathy; Proteasome inhibitors