Mechanisms of drug resistance to proteasome inhibitors in multiple myeloma cells

Multiple myeloma is a malignancy originating from terminally differentiated B-lymphocyte-plasma cells that produce large amounts of an abnormal paraprotein observed in the blood/urine. The annual incidence of multiple myeloma worldwide is 1% of all malignancies, and 10-15% of all hematological malignancies. Despite significant advances in treatment, multiple myeloma is still a challenging disease to diagnose and treat (15). Current treatment protocols have increased the 5-year survival rate of myeloma patients by more than 50%. In10% of patients, complete remission may last for many years, while in others, MM may relapse early or fail to respond to therapy. In the past 10 years, new anti-myeloma drugs from different pharmacological classes, such as proteasome inhibitors (e.g., bortezomib, carfilzomib and ixazomib), immunomodulatory drugs iMiD (e.g., lenalidomide, pomalidomide), and monoclonal antibodies (e.g., daratumumumab) have been approved.