The Warburg Effect and the Hallmarks of Cancer

Abstract

It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the hallmarks of cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure. This increased pressure is responsible for the fractal shape of the tumor, the secretion of collagen by the fibroblasts and plays a critical role in metastatic spread. The massive extrusion of lactic acid contributes to the extracellular acidity and the activation of the immune system. The decreased oxidative phosphorylation leads to impairment in CO2 levels inside and outside the cell, with increased intracellular alkalosis and contribution of carbonic acid to extracellular acidosis-mediated by at least two cancer-associated carbonic anhydrase isoforms. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Mitochondrial disappearance (such as seen in very aggressive tumors) is a consequence of mitochondrial swelling, itself a result of decreased ATP concentration. The transmembrane pumps, which extrude, from the mitochondria, ions, and water, are ATP-dependant. Therapy aiming at increasing both the number and the efficacy of mitochondria could be very useful.

miR‐128‐3p contributes to mitochondrial dysfunction and induces apoptosis in glioma cells via targeting pyruvate dehydrogenase kinase 1

“…A classical metabolic adaptation of tumor cells is a shift to aerobic glycolysis as a main source of adenosine triphosphate (ATP), rather than oxidative phosphorylation (OXPHOS), a phenomenon referred to as the Warburg effect. 5,6 Glioma, like most cancers, shows intensive glycolysis and lactic acidosis, presents a unique metabolic state known as the Warburg effect, where cancer cells utilize aerobic glycolysis as the primary supplier of ATP. 7 The Warburg effect is the most important alteration in cancer cell metabolism, which is characterized by excessive glycolysis and increase in glycolytic enzymes.…”

Chlorine dioxide as a possible adjunct to metabolic treatment

“…This inhibition appears to be independent of the primary tumor site and has been reproduced in different laboratories 40,41 .…”

Enhanced glucose metabolism mediated by CD147 is associated with 18F‐FDG PET/CT imaging in lung adenocarcinoma

“…Thus, cancer cells exhibit increased glucose uptake and an enhanced glycolysis rate even in the presence of oxygen. 7 The widespread application of 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET) imaging in initial and differential tumor diagnoses, clinical staging, and therapeutic effect evaluation utilizes the hallmarks of upregulated glycolysis in tumor cells. 8,9 Therefore, 18 F-FDG PET data have emphasized the sheer preponderance of elevated glucose trapping in cancer.…”