title: Oxidative stress and proteasome inhibitors in multiple myeloma.
abstract: Multiple myeloma is a form of plasma cell neoplasm that accounts for approximately 10% of all hematological malignancies. Recently, several novel drugs have been discovered that almost doubled the overall survival of multiple myeloma patients. One of these drugs, the first-in-class proteasome inhibitor bortezomib (Velcade) has demonstrated remarkable response rates in multiple myeloma patients, and yet, currently this disease remains incurable. The major factor undermining the success of multiple myeloma treatment is a rapidly emerging resistance to the available therapy. Thus, the development of stand-alone or adjuvant anti-myeloma agents becomes of paramount importance. Overproduction of intracellular reactive oxygen species (ROS) often accompanies malignant transformation due to oncogene activation and/or enhanced metabolism in tumor cells. As a result, these cells possess higher levels of ROS and lower levels of antioxidant molecules compared to their normal counterparts. Unbalanced production of ROS leads to oxidative stress which, if left unchecked, could be toxic for the cell. In multiple myeloma cells where high rates of immunoglobulin synthesis is an additional factor contributing to overproduction of ROS, further induction of oxidative stress can be an effective strategy to cope with this disease. Here we will review the available data on the role of oxidative stress in the cytotoxicity of proteasome inhibitors and the use of ROS-inducing compounds as anti-myeloma agents.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Electronic address: Brittany.lipchick@roswellpark.org.
authors.forename: Brittany C
authors.initials: BC
authors.lastname: Lipchick
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Fink
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Nikiforov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species
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