Oxidative Stress in Multiple Myeloma Pathophysiology and Treatment

Abstract

Multiple myeloma (MM) is a clonal plasma cell proliferation disease characterized by an abnormal monoclonal protein, leading to specific-organ damage. Nowadays, significant knowledge about the pathophysiology and the treatment of MM has been gained. Unique lesions regarding reactive oxygen species (ROS) and reactive nitrogen species (RNS) production in MMs pathobiology have been reported due to new technologies. On the one hand, in most stages of MM, an overproduction of free radicals and a deregulation of the human antioxidant system can be found, leading to intense myeloma cell proliferation. On the other hand, in advanced disease with comorbidities, oxidative stress suppression leads to further growth of neoplastic clone. Novel agents that have been emerged for MM treatment, such as proteasome inhibitors, immunomodulatory drugs, epigenetic drugs and monoclonal antibodies have improved patients survival and quality of life. These drugs increase oxidative stress, resulting in myeloma cell apoptosis, via activation of a molecular pathway called Unfolded Protein Response (UPR). Nowadays, the research focuses on the discovery of novel factors that can enhance their anti-myeloma effects, by modulation of oxidative stress.