title: Proteasome inhibitors in cancer therapy: Treatment regimen and peripheral neuropathy as a side effect.
abstract: Proteasomal system plays an important role in protein turnover, which is essential for homeostasis of cells. Besides degradation of oxidized proteins, it is involved in the regulation of many different signaling pathways. These pathways include mainly cell differentiation, proliferation, apoptosis, transcriptional activation and angiogenesis. Thus, proteasomal system is a crucial target for treatment of several diseases including neurodegenerative diseases, cystic fibrosis, atherosclerosis, autoimmune diseases, diabetes and cancer. Over the last fifteen years, proteasome inhibitors have been tested to highlight their mechanisms of action and used in the clinic to treat different types of cancer. Proteasome inhibitors are mainly used in combinational therapy along with classical chemo-radiotherapy. Several studies have proved their significant effects but serious side effects such as peripheral neuropathy, limits their use in required effective doses. Recent studies focus on peripheral neuropathy as the primary side effect of proteasome inhibitors. Therefore, it is important to delineate the underlying mechanisms of peripheral neuropathy and develop new inhibitors according to obtained data. This review will detail the role of proteasome inhibition in cancer therapy and development of peripheral neuropathy as a side effect. Additionally, new approaches to prevent treatment-limiting side effects will be discussed in order to help researchers in developing effective strategies to overcome side effects of proteasome inhibitors.
authors.affiliation: Department of Biochemistry, School of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, 34854 Maltepe, Istanbul, Turkey.
authors.forename: Gulce Sari
authors.initials: GS
authors.lastname: Kaplan
authors.affiliation: Department of Biochemistry, School of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, 34854 Maltepe, Istanbul, Turkey.
authors.forename: Ceyda Corek
authors.initials: CC
authors.lastname: Torcun
authors.affiliation: Department for Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.affiliation: Department of Biochemistry, School of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, 34854 Maltepe, Istanbul, Turkey.
authors.forename: Nesrin Kartal
authors.initials: NK
authors.lastname: Ozer
authors.affiliation: Department of Biochemistry, School of Medicine/Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, 34854 Maltepe, Istanbul, Turkey. Electronic address: betulkarademir@marmara.edu.tr.
authors.forename: Betul
authors.initials: B
authors.lastname: Karademir
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D059748:Proteolysis
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex
keywords: Bortezomib; Carfilzomib; Chemotherapy; Neuropathy; Proteasome