Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies

Huaming      Sheng; Ben      Niu; Hongbin      Sun

Abstract

Multiple lines of evidence shows that tumorigenesis is often associated with altered carbohydrate metabolism, characterized by increased glucose uptake and elevated glycolysis, which was first recognized by Otto Warburg 70 years ago. Therefore, the inhibition of glycolysis has been proposed as a therapeutic strategy for cancer treatment. However, this disordered glycotic process does not represent the whole picture of altered energy metabolism during cancer cell transformation. In order to achieve rapid cell proliferation, tumor cells have to constantly accumulate large amount of macromolecules for replication, which has led to several hallmarks of cancer demonstrating its robust metabolic adaptation, including high levels of aerobic glycolysis rate, high rate of energy-consuming processes for syntheses of proteins, DNA and fatty acids. This review summarizes some potential drugable targets as well as their pharmacological inhibitors in glucose, glutamine and fatty acid metabolic pathways. In addition, the upstream oncogenic signaling pathways that are tightly in conjunction with the altered metabolism in tumors are also covered.

Keywords: Tumor energy metabolism, glucose, glutamine, fatty acid, oncogenic signals, metabolic interference