Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance

SIMPLE SUMMARY: Multiple myeloma (MM) is a common blood cancer that affects plasma cells, a type of immune cell found in bone marrow. Treatment options for MM have improved in recent years, but most patients eventually become resistant to existing therapies, highlighting the need for better treatments. MM cells alter their cellular metabolism to fuel growth and survival and can further adapt their metabolism to promote drug resistance. Here we review the metabolic changes that occur in MM and in the development of resistance to proteasome inhibitors, a common MM therapy, and discuss opportunities for therapeutic intervention. ABSTRACT: Despite significant improvements in treatment strategies over the past couple of decades, multiple myeloma (MM) remains an incurable disease due to the development of drug resistance. Metabolic reprogramming is a key feature of cancer cells, including MM, and acts to fuel increased proliferation, create a permissive tumour microenvironment, and promote drug resistance. This review presents an overview of the key metabolic adaptations that occur in MM pathogenesis and in the development of resistance to proteasome inhibitors, the backbone of current MM therapy, and considers the potential for therapeutic targeting of key metabolic pathways to improve outcomes.