Metabolomics in oncology – A fascinating travel into the mechanisms of metabolic disturbances during carcinogenesis

Abstract

cancerous transformation, among them cellular metabolism. Intrinsic and extrinsic factors, such as environmental and genetic factors, play a key role in the metabolic pathway alterations of cancer cells and contribute to the oncogenic processes altering the cellular phenotype and molecular physiology (1, 2). Metabolomics is the large-scale study of small molecules, known as metabolites. Collectively, these small molecules and their interactions within a biological system are known as the metabolome. Metabolomics are currently used in biomarker identification for the diagnosis and prognosis of cancer and can play a crucial role in the evaluation of therapeutic interventions (3, 4). The most prominent alteration in cancer cell metabolism is the phenomenon called “Warburg effect” or aerobic glycolysis. Cancer cells uptake glucose that in the presence of oxygen is not used through the Krebs cycle, but is instead incompletely oxidized or fermented to lactate. Unlike other oncogenic pathways that can be completely abrogated by using small molecular inhibitors or antibodies, this is not applicable to fundamental metabolic pathways. The latter would have immediate detrimental effects to the whole organism. Targeting through the level of enzymatic activity of nodal enzymes in metabolic pathways could provide therapeutic opportunities. Metabolomics can help us to identify the exact processes which a cancer cell can use a biological molecule (such as glucose) in order to produce energy or all the other essential biological molecules (such as nucleotides, lipids, and amino acids) (6)(7). Metabolomics could have several applications in oncology. Metabolomics can be used for the development of sensitive biomarkers to help in early diagnosis of several tumors. For example, the metabolic profile in urine samples could be used for the early and precise diagnosis of renal carcinoma, which is a tumor that is often diagnosed at advanced stages (8). In ovarian cancer, metabolomics can be used in order to detect the metabolic profile of serum proteins, which is different from the metabolic profile in healthy postmenopausal women (9). Also, prostate cancer cells carry alterations in their metabolites, such as increased amounts of phosphatidylcholine and decreased amounts of branched amino acids (10). Metabolomics can also assist to develop new therapeutic interventions for several tumors. A decade ago it was shown that mutations in the isocitrate dehydrogenase 1 enzyme (IDH1) lead to the intracellular accumulation of the metabolite 2-hydroxyglutarate (2HG) (11). 2HG contributes to the malignant transformation of glial cells. Currently, IDH1/2 inhibitors – namely ivosidenib and enasidenib – have been approved for patients with relapsed or refractory acute myeloid leukemia. Cervical cancer is another area that the use of metabolomics could have therapeutic implications. Through this Forum of Clinical Oncology