Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Multiple myeloma is a cancer of plasma cells causing bone fractures, anemia, renal insufficiency and hypercalcemia. Despite the introduction of new drugs in the past years, it still remains incurable and most patients die from the disease. Multiple myeloma cells are characterized by the production of high amounts of monoclonal antibodies. Therefore, maintaining protein homeostasis from synthesis through folding to degradation is crucial for multiple myeloma cells. While protein ubiquitination and organized degradation are typically considered critical for cellular health, an emerging strategy is to block these processes to induce cell death in disease-state cells characterized by protein over-production. Recent development of compounds that alter the ubiquitin proteasome pathway and drugs that affect ubiquitin-like modifications appear promising in both preclinically and in clinical trials. This review summarizes the impact of protein modifications such as ubiquitination and ubiquitin-like modifications in the biology of multiple myeloma and how it can be exploited to develop new effective therapies for multiple myeloma.