Molecular Biomarkers & Diagnosis

Targeting Tumor Metabolism: A Biochemical Explanation Related to A Systems Biology Lipidomics Based Approach

Abstract

Vincent van Ginneken

This mini-review presents the current state of our knowledge of biomarkers in the selected oncology research area of “adipose tumors”: lipomas (benign) and liposarcomas. (malign). To our awareness never before have clear arguments been given underpinning a hypothesis that convincingly stated that malignant transformation from a lipoma can occur towards a liposacroma based on a biochemical model. Acidic pH-due to lactic acid- derived from cancer cells may induce failed reprogramming of normal differentiated cells adjacent tumor cells and turn them into cancer cells. An important observation at this cellular response of aerobic fermentation (“Warburg effect”) is that it occurs already at pre-carcinogenic conditions so it has another major aiming, we hypothesize to maintain the redox balance in combination with glutaminolysis and reversed β-oxidation in order to keep the Krebs cycle spinning. This peculiar observation convinced us-after studying obesity and two novel biomarkers for type 2 diabetes-that most cancers are a metabolic and redox balance disease. In addition, we describe the present role of Lipoproteins like cholesterol as carrier of anti-cancer medicine but hypothesize simultaneously that “fat particles” carried by lipoproteins can result in metastasis of “lipid tumors”. We give four demands for a suitable biomarker-not only for a metabolomics based on a lipidomics based approach-but in general. The final culprit of this review is the biochemical model for this 36:1 phosphatidylcholine biomarker which was not only found in all non-adipose tissue but also in the blood. Hypoxic conditions in white adipose tissue (WAT) either during obesity, either in the microenvironment of an adipose tumor will result in further growth based of fatty acid (FA) chain elongation based on a reversal of the β-oxidation under hypoxia in order to maintain the redox balance and keep the Krebs cycle spinning.