Metabolism describes all catabolic and anabolic reactions that fulfill bioenergetic and biosynthetic needs of an organisms/ a cell to maintain life. Metabolism is largely determined by the availability of nutrients (over-, under- or mal-nutrition) and the functional requirements of the body (e.g. physical activity versus sleeping). On the cellular level, the vascularization (essential nutrients are delivered to the cell by the blood flow) the cellular state (e.g. proliferation versus quiescence) or specialized cellular functions determine cellular metabolism. It has been noted a century ago by Otto Warburg that cancer cell metabolism differs significantly from the metabolism of non-malignant cells in terms of the preferential usage of anaerobic glycolysis even under well-oxygenated conditions. As the fermentation of glucose is less energy efficient than oxygen-dependent glucose respiration by mitochondria, cancer cells are in need to increase their glucose uptake. This metabolic feature is widely used as a diagnostic imaging method in 18F-fluorodeoxyglucose (18F-FDG) positron emission to detect growing cancerous lesions (including metastasis). Extensive efforts to explain the paradox of the Warburg effect revealed complex metabolic alterations in cancers that allow them to rapidly produce energy, increase the biosynthesis of macromolecules and balance their redox state even under adverse environmental conditions where nutrient and oxygen supply varies. More recently it has been recognized that cancers are heterogeneous regarding their metabolic programs and the possibility that more aggressive cancer cell subpopulations like cancer stem cells, metastasizing cells or therapy resistant clones are more dependent on specific metabolic programs is being evaluated for therapeutic purposes.
Did you know that in vivo metabolic flow analysis of human cancers demonstrated significant heterogeneity regarding metabolic programs?
Did you know that mitochondria were considered inactive in cancer for almost a century whereas today it´s clear that they play a major role on cancer?
Did you know that according to in vivo studies in patients as well as in mice both, glycolysis and oxidative glucose metabolisms are increased in tumors compared to non-malignant tissue.