Thank you for your observation. I couldn't agree with you more. Our current pursuit is to dissect those biochemical details that conform to the altered fluxes and entropy that you have mentioned.

I am sorry, you is wrong because your sentence is nonsense. Just your current pursuit can not altered Entropy, i.e. altered Second law of thermodynamics. It is meant altered Science Thermodynamics.

Dear Michail,

The evidence from Warburg's studies were that even under aerobic conditions, cancer cells preferentially use glycolysis rather than the more efficient oxidative phosphorylation pathway. However, cancer cells inside solid tumours predominantly exist under anaerobic, hypoglycemic and acidic conditions and these stressors cause major changes to the cell energy metabolism that were not considered by Warburg because they were not known about. As for the effect of these stressors on the thermodynamics, we are not experts in that area. We are more concerned with the scientific basis, at the molecular level, underlying the altered energy metabolism in cancer cells and its effects on their surivival.

More recent evidence reviewed in our published articles supports a key role for residual mitochondrial function as essential for survival of cancer cells. This was also implied by Warburg's findings. More recently, for example, it has been shown that Rho zero (mtDNA deficient) cancer cells do not form tumours until they regain their mitochondria. The effects of hypoxia and activation of the HIFs among other factors, cause gross changes to cellular energy metabolism, including glycolysis and the oxidative pentose phosphate pathways. The result is to significantly modify energy metabolism and the redox state that exists in cancer cells to support their continued growth and survival. The more important point extending from these studies is that the mitochondria are excellent targets for anticancer therapy.

Dear Stephen,

Firstly, I can not agree with your definition cancer metabolism as stressors cause in anaerobic state as hypoglycemic and acidic conditions because it is known that as glycolysis as well as Krebs tricarboxylic acids cycle occur as anaerobic processes in acidic condition in norm. Cancer metabolism exhibits excessive shift into huge anabolic processes for exerting excessive proliferative processes of growth tumor which is realized via great glycolysis processes and can not- be characterized as stressor cause, i.e. unclear "what processes' stressor cause is it". Concerning to cancer metabolism, see following article: Ponisovskiy M.R., (2010), “Cancer metabolism and the Warburg effect as anabolic process outcomes of oncogene operation”, Critical Reviews in Eukaryotic Gene Expression, 20 (4), 325 – 339.

Secondly, "aerobic glycolysis" of Warburg effect does not except anaerobic condition of development cancer abundance anabolic biosynthetic processes which use glycolysis and great aerobic processes of cytochrome c in mitochondria (see Ponizovskiy M.R., (2013), Biophysical and biochemical transmutation of mitochondrial function in cancer genesis, Biochemistry & Analytical Biochemistry, Volume 2, Issue 3, 1 – 9, doi:10.4172/2161-1009.1000137).

Thirdly, You don't understand thermodynamics writing "these stressors on the thermodynamics, we are not experts in that area".

Warburg effect on cancer cells is not limited just for energy supply, but also cancer cells utilized its residuals for producing amino acid. besides, I think cancer cell utilize residual for signal transduction in tumor weird web as well. moreover, cancer surrender cell does have an impact on cancer cells metabolism pathways, for instance, CAF cells metabolic pathway's effects on cancer metabolic pathway has been proved(they have kinda synchronization, which contributed to cancer cells fast/slow growing or highly/rarely metastasis).

Dear Pajman,

Producing abundance quantity amino acids and other substances occur via anabolic endergonic biosynthetic processes of cancer processes which require a lot of energy supply in cancer metabolism. That is crucial mechanism of each cancer metabolic pathway which determine Warburg effect mechanism as "aerobic glycolysis". However multiple metabolic pathways in cancer processes are supplemental bifurcations of anabolic endergonic biosynthetic processes to this cricial mechanism of Warburg effect forming multiple forms of cancer as well as Pasteur effect for able-bodied tissue metabolism.

Dear Dr. Michail R Ponizovskiy

amino acid generation for cancer cells does consume much energy (those cells don't care about it). as far as I know, a tumor contains at least two different cells, cancer associate cells (CACs)(bystanders) and cancer stem cells(CSCs). the web between these cells is highly tangible due to extracellular matrices, recruited cells, etc. but the bottom line is, energy production between these cells are highly linked to unrelated stuff, for example, pyruvate existence effect on proper collagen production or CACs assign metabolic pathways in CSCs in some cancer.

sincerely yours,

pejman

Please, read carefully my previous answer concerning to Warburg effect. Besides piruvate is the main Reagent in Glycolysis and does not take part in collagen production (see Ponisovskiy M.R., (2010), “Cancer metabolism and the Warburg effect as anabolic process outcomes of oncogene operation”, Critical Reviews in Eukaryotic Gene Expression, 20 (4), 325 – 339 ). Further, I know only cancer cells of different morphology.in different tissues as well as cancer stem cells, but I don't know cancer associate cells. What is it?

-Not production, but proper collagen: in this article professor, Sarah-Maria Fendt proved that ''pyruvate uptake induces the production of α-ketoglutarate. This metabolite, in turn, activates collagen hydroxylation by increasing the activity of the enzyme collagen prolyl-4-hydroxylase (P4HA). Inhibition of pyruvate metabolism was sufficient to impair collagen hydroxylation and consequently the growth of breast-cancer-derived lung metastases in different mouse models. in short, they found a causal relation between collagen remodelling and the nutrient environment in the metastatic niche.

-Thanks for the review article.

-associate cells means those cells that underpin cancer, such as cancer-associated fibroblasts (CAF) , CTC–neutrophil clusters, and stem cells etc.

Article Breast cancer cells rely on environmental pyruvate to shape ...

Thank you for the article. I have familiarized myself with Abstract of this article which was studied role environmental matrix of cancer cells and metastatic niche via hydroxyliated collagen, i.e. modificated collagen but not production collagen. This interesting work does not reject above presented cancer metabolism mechanism as "aerobic glycolysis" of Warburg effect.