Glycolysis and glutaminolysis not only provide cancer cells with ATP from the readily available substrates glucose and glutamine, but their rapid energy flux can also provide cancer cells with the necessary substrates and metabolic intermediates for lipid, amino acid and DNA synthesis that are needed for growth.
Notably cancer cells produce far less ATP per molecule of glucose, though nevertheless, they can produce ATP at a much faster rate due to rapid consumption of substrates.
Cancer cells produce ATP almost a hundred times faster than normal cells.
Cancer cells actively produce more glucose transporters on their cell surface membranes, so that more glucose is brought inside the cell. This increase in glucose metabolism through glycolysis allows the generation of glycolytic intermediates that funnel into biosynthetic pathways that support the production of NADPH, lipids, proteins and nucleotides.
Mitochondria are continually confronted with factors that can jeopardize how well they function. These factors include: chronic stress, sleep disturbances, hyperglycemia, xenobiotics such as drugs, antibiotics, organic pollutants and environmental toxins.
These factors can cause mitochondrial dysfunction, which can be characterized by any of four ways; (a) insufficient number of mitochondria, (b) insufficient substrate or nutrient co-factors needed for oxidative phosphorylation, (c) acquired dysfunction in the ATP synthesis machinery, or (d) damage to the mitochondrial membranes.
Mitochondrial dysfunction results in a number of cellular consequences, including: (i) decreased ATP production; (ii) increased reliance on alternative anaerobic energy sources; and (iii) increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS).
Hence, with this understanding of the fundamental biology of tumor energy production in mind, treatment regimens which address this phenomenon directly, constitute the next step in delivering effective and sustainable Oncology therapies to patients.
