Abstract

Altered metabolic regulation has long been observed in human cancer and broadly used in the clinic for tumor detection. Two recent findings—the direct regulation of metabolic enzymes by frequently mutated cancer genes and frequent mutations of several metabolic enzymes themselves in cancer—have renewed interest in cancer metabolism. Supporting a causative role of altered metabolic enzymes in tumorigenesis, abnormal levels of several metabolites have been found to play a direct role in cancer development. The alteration of metabolic genes and metabolites offer not only new biomarkers for diagnosis and prognosis, but also potential new targets for cancer therapy.

Introduction

Otto Warburg observed more than 80 years ago that tumor cells have altered metabolic regulation; despite having an increased uptake of glucose, tumor cells produce much less ATP than expected from a complete tricarboxylic acid (TCA) cycle coupled to oxidative phosphorylation, and instead accumulate a significant amount of lactate [1–۴]. Although the molecular mechanisms and significance of this shift to aerobic glycolysis in tumor cells, commonly known as the Warburg Effect, remain poorly understood, enhanced glucose uptake provides the basis for 18FDG-PET technology which has been widely used clinically for tumor detection by injecting patients with a radio-labeled glucose analog, 2(18F)- fluoro-2-deoxy-D-glucose (FDG), followed by imaging with positron emission tomography (PET).