Metabolic alterations and the potential for targeting metabolic pathways in the treatment of multiple myeloma

Abstract

Metabolism is defined as the collection of complex biochemical processes that living cells use to generate energy and maintain their growth and survival. Metabolism encompasses the synthesis and breakdown of glucose, fatty acids, and amino acids; the generation of energy (ATP); and oxidative phosphorylation. In cancer cells, metabolism can be commandeered to promote tumor growth and cellular proliferation. These alterations in metabolism have emerged as an additional hallmark of various cancers. In this review we focus on metabolic alterations in multiple myeloma (MM) - a malignancy of plasma cells - including derangements in glycolysis, gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid/amino acid synthesis and degradation. Particular focus is given to metabolic alterations that contribute to myeloma cell growth, proliferation and drug resistance. Finally, novel approaches that target metabolic pathways for the treatment of MM are discussed.

Keywords: Metabolism; alterations; multiple myeloma; treatment.

Figure 1.

Summary of the metabolic changes in multiple myeloma cells and in resistant myeloma cells