Abstract
A clear understanding of the origins of cancer is the basis of successful strategies for effective cancer prevention and management. The origin of cancer at the molecular and cellular levels is not well understood. Is the primary cause of the origin of cancer the genomic instability or impaired energy metabolism? An attempt was made to present cancer etiology originating from life's major evolutionary transition. The first evolutionary transition went from simple to complex cells when eukaryotic cells with glycolytic energy production merged with the oxidative mitochondrion (The Endosymbiosis Theory first proposed by Lynn Margulis in the 1960s). The second transition went from single-celled to multicellular organisms once the cells obtained mitochondria, which enabled them to obtain a higher amount of energy. Evidence will be presented that these two transitions, as well as the decline of NAD+ and ATP levels, are the root of cancer diseases. Restoring redox homeostasis and reactivation of mitochondrial oxidative metabolism are important factors in cancer prevention.
Highlights
Could cancer causation be interpreted as an allegory not to the damaged hardware but to an incorrect function of a software? Do we thence use wrong approaches to treat the cancer disease with chemotherapy and radiation therapy, which are aimed at destroying the hardware, instead of a more sophisticated approach aimed at reprogramming the software inside the cells in order to restore the normal mitochondrial function and metabolism?
Aerobic glycolysis of tumors is in some measure displayed by activation of oncogenes or absence of tumor suppressors, which are intensified by stabilization of the hypoxia-inducible factor (HIF) [15], which encodes for all of the glycolytic enzymes
Cancer cells shift their metabolism toward glycolysis, a strategy that allows for their survival when oxygen is limited [17], and Oxidative Medicine and Cellular Longevity increase the availability of biosynthetic intermediates needed for cellular growth and proliferation [18]
Summary
Could cancer causation be interpreted as an allegory not to the damaged hardware (damaged genetic material caused by chance mutation) but to an incorrect function of a software (a metabolic program)? Do we thence use wrong approaches to treat the cancer disease with chemotherapy and radiation therapy, which are aimed at destroying the hardware (killing cells), instead of a more sophisticated approach aimed at reprogramming the software inside the cells in order to restore the normal mitochondrial function and metabolism?. Aerobic glycolysis of tumors is in some measure displayed by activation of oncogenes or absence of tumor suppressors, which are intensified by stabilization of the hypoxia-inducible factor (HIF) [15], which encodes for all of the glycolytic enzymes It seems that fully operating mitochondria regulate apoptosis by releasing cytochrome c [16] and suppressing genes of cancer-like metabolism, which have been conserved from 500,000 million years ago and persist in cells of multicellular organisms. Is cancer caused by damaged mitochondria (impaired mitochondrial function) and metabolic dysfunction, which activates the divergence of the glucose metabolism away from the energy production and stimulates cell growth (transition from oxidative phosphorylation to glycolysis/fermentation)? According to Seyfried et al [57, 58], the missing link in Warburg’s theory is the succinic acid fermentation which uses glutamine as a major substrate through sequential conversion of glutamine → glutamate → alpha‐ketoglutarate → succinyl‐CoA → succinate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
