Cancer as a metabolic disease: implications for novel therapeutics

Abstract

Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology.

Hyperinsulinemia and Insulin Resistance: Scope of the Problem

“…Thus, they are unable to generate ATP efficiently via oxidative phosphorylation and instead revert to rampant glycolysis and a more primitive form of energy generation: 'aerobic fermentation' -fermentation even in the presence of oxygen, known as the Warburg effect. 44,45,46,47 With significant impairment in cancer cells' capacity to oxidise fatty acids and ketones, IR and chronic hyperglycaemia provide cancer cells with a large and continuous supply of the fuel substrate they metabolise most effectively: glucose. 48 In addition, chronic hyperinsulinemia may promote carcinogenesis via stimulation of insulin-like growth factor 1 (IGF-1), modulation of sex hormones and through promotion of inflammation.…”

“…The resulting oxidative stress leads to eventual mitochondrial dysfunction or destruction, which has been implicated in the pathology or progression of conditions not typically associated with IR, such as multiple sclerosis, 63,64,65 AD, 66,67 Parkinson's disease 68,69 and cancer. 44,70 Chronic hyperinsulinemia may promote systemic inflammation, 71 in part by influencing desaturase enzymes involved in the inflammatory process (via catalysing the conversion of omega-6 linoleic acid into inflammatory prostaglandins and other signalling molecules). 72 Chronic, unresolved inflammation and oxidative stress are increasingly recognised as underlying factors in atherosclerosis and other forms of heart disease.…”

Elucidating the Mode of Action of Marine Natural Products through an Immunoaffinity Fluorescent (IAF) Approach

“…16 The reprogramming of energy metabolism in cancer cells is recognized as an important feature for tumor progression since the description of the "Warburg effect". 36 Cancer cells are highly dependent of glycolytic pathways in spite of oxygen supply to keep their constant proliferative state, and this 'adaptive' condition raises from higher expression in key proteins such as glucose transporters GLUTs, and enzymes like GAPDH, ENO1, hexokinase II (HKII), lactate dehydrogenase (LDH) and phosphofructokinase (PFK-B). 37 Hence, these proteins have been explored with some success as therapeutic targets for cancer treatment.…”

Keton cisimlerinin insan meme kanseri hücrelerinde (MCF-7) canlılık üzerine etkileri

“…Mitochondrial pathology observed in cancer cells include decreased number of mitochondria, swelling, mutations in mtDNA, altered membrane potential and abnormal enzyme presence or function [2][3][4]. All of these defects in mitochondrial structure and function weaken respiratory capacity and make it difficult to rely on substrate-level phosphorylation for survival [5]. Ketone bodies are metabolized only in mitochondria, thus cancer Ketone bodies and breast cancer Marmara Medical Journal 2018; 31: 57-60 cells with mitochondrial dysfunction cannot efficiently metabolize them for energy [6].…”