A review of applications of metabolomics in cancer

Abstract

Cancer is a devastating disease that alters the metabolism of a cell and the surrounding milieu. Metabolomics is a growing and powerful technology capable of detecting hundreds to thousands of metabolites in tissues and biofluids. The recent advances in metabolomics technologies have enabled a deeper investigation into the metabolism of cancer and a better understanding of how cancer cells use glycolysis, known as the "Warburg effect," advantageously to produce the amino acids, nucleotides and lipids necessary for tumor proliferation and vascularization. Currently, metabolomics research is being used to discover diagnostic cancer biomarkers in the clinic, to better understand its complex heterogeneous nature, to discover pathways involved in cancer that could be used for new targets and to monitor metabolic biomarkers during therapeutic intervention. These metabolomics approaches may also provide clues to personalized cancer treatments by providing useful information to the clinician about the cancer patient's response to medical interventions.

Figure 1

General flow chart of a typical metabolomics experiment in a cancer study.

Figure 2

Energy and metabolic pathways and associated protein enzymes and transporters active in cancer. Metabolite abbreviations: αKG, α-ketoglutarate; FBP, fructose 1,6-diphosphate; NADP, nicotinamide adenine dinucleotide phosphate; NADPH, reduced form of nicotinamide adenine dinucleotide phosphate; OAA, oxaloacetate; PEP, phosphoenol pyruvate; PYR, pyruvate. Protein abbreviations: ATPCL, ATP citrate lyase; CA, carbonic anhydrase; FASN, fatty acid synthase; GLUT, glucose transporter; GLNT, glutamine transporter; G6PD, glucose-6-phosphate dehydrogenase; HK, hexokinase; LDH, lactate dehydrogenase; MCT, monocarboxylate transporter; NHE1, Na⁺/H⁺ exchanger; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase; PK, pyruvate kinase; SDH, succinate dehydrogenase; TK/TA, transketolase/transaldolase.