More Than Meets the Eye Regarding Cancer Metabolism

Abstract

In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not “give up” on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.

Searching for the Metabolic Signature of Cancer: A Review from Warburg’s Time to Now

“…The current description taken from the scientific literature, in its broad sense, varies according to the authors, some dwelling more on the production of lactate [ 52 ], others on the transition from one type of metabolism to another [ 53 ], but generally corresponds to the idea of deregulation of the metabolism towards aerobic glycolysis . This definition, in itself, does not appear to pose too many problems because it underlies several premises that are sometimes stated, sometimes not, but which should be clarified (the list is not exhaustive), as follows: Healthy cells primarily use respiration to generate ATP in the presence of oxygen [ 54 , 55 ]. Healthy cells make little use of fermentation in the presence of oxygen because ATP is sufficiently produced by respiration [ 55 ].…”

“…This definition, in itself, does not appear to pose too many problems because it underlies several premises that are sometimes stated, sometimes not, but which should be clarified (the list is not exhaustive), as follows: Healthy cells primarily use respiration to generate ATP in the presence of oxygen [ 54 , 55 ]. Healthy cells make little use of fermentation in the presence of oxygen because ATP is sufficiently produced by respiration [ 55 ]. If lactate production is high in the absence of oxygen, this is normal since the cell must produce ATP to survive.…”

“…Healthy cells make little use of fermentation in the presence of oxygen because ATP is sufficiently produced by respiration [ 55 ].…”

SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

“…During normal glycolysis, glucose is metabolized into pyruvate, transferred into the mitochondria, where it is catabolized in the tricarboxylic acid cycle (TCA) and fuels oxidative phosphorylation to generate large amounts of ATP [ 12 ]. Viruses and tumors can alter cellular metabolism and increase pyruvate conversion into lactate in the presence of oxygen, a phenomenon commonly referred to as the Warburg effect [ 13 ].…”

Editorial: Metabolite and Nutrient Transporters in Cancer-Cell Metabolism: Role in Cancer Progression and Metastasis

“…There has been a noticeable surge of interest in cancer-cell metabolism. In order to support their specific metabolic needs and rapid proliferation, cancer cells not only enhance the rates of normal metabolic pathways but also short-circuit and/or substantially modify other metabolic pathways ( Ganapathy-Kanniappan, 2018 ; Kubicka et al, 2021 ; Vaupel and Multhoff, 2021 ; Pavlova et al, 2022 ). These changes are carried out through induction or suppression of specific enzymes and also through mutations in particular enzymes.…”