Metabolic Vulnerabilities in Multiple Myeloma

SIMPLE SUMMARY: The advent of novel therapeutics has revolutionized the therapeutic scene of multiple myeloma (MM) and improved clinical outcomes significantly. Nonetheless, the disease remains incurable, especially in patients with refractory and relapsed disease. The emerging field of cancer metabolism has revealed metabolic vulnerabilities that can be exploited in myeloma. Altered glucose and glutamine metabolism are the most well-studied pathways in MM. In this review, we provide further insights into the scope of research that has been recently extended to these and other metabolic pathways and their implications for the disease and the tumor microenvironment. We also discuss some potential impacts of metabolism on myeloma prognosis and highlight mechanisms of drug resistance. Considering the challenges that abound, we deliberate on future knowledge gaps worth addressing. ABSTRACT: Multiple myeloma (MM) remains an incurable malignancy with eventual emergence of refractory disease. Metabolic shifts, which ensure the availability of sufficient energy to support hyperproliferation of malignant cells, are a hallmark of cancer. Deregulated metabolic pathways have implications for the tumor microenvironment, immune cell function, prognostic significance in MM and anti-myeloma drug resistance. Herein, we summarize recent findings on metabolic abnormalities in MM and clinical implications driven by metabolism that may consequently inspire novel therapeutic interventions. We highlight some future perspectives on metabolism in MM and propose potential targets that might revolutionize the field.