Actionable Metabolic Pathways in Heart Failure and Cancer-Lessons From Cancer Cell Metabolism

Abstract

Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

Keywords: cancer cell metabolism; cardiac metabolism; clinical trials as topic; heart failure; intermediary metabolism; metabolic targets; systems biology; targeted treatments.

Figure 1

Targeting metabolic enzymes as a strategy in heart failure and cancer. Central metabolic pathways and the involvement of key metabolic enzymes in the synthesis of macromolecules are depicted (shown in gray boxes). α-KG, α-ketoglutarate; G6P, glucose-6-phosphate; GLS, glutaminase; GLUT1, glucose transporter type 1; Glut, glutamate; Gln, glutamine; HK-II, hexokinase II; I, complex I; III, complex III; IV, complex IV; MCT, monocarboxylate transporter; OAA, oxaloacetate; PC, pyruvate dehydrogenase complex; PDK, pyruvate dehydrogenase kinase; Succ, succinate V, complex V.