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Jcancom
(@jcancom)
Joined: 3 years ago
Posts: 434
31/07/2020 3:20 am  

There are just so many complex and convoluted aspects of cancer metabolism that provide potentially new avenues of vulnerability. This article helps to redefine the purpose of respiration. Isn't the purpose of respiration obvious in cancer? Recycle NADH, make ATP, maintain an electrochemical gradient in the matrix etc.? This is fairly basic and presumably firmly established science. Yet, perhaps there is an until now hidden reason behind OXPHOS ... support asparate biosynthesis? If so, then selectively inhibiting OXPHOS along with supression of the asparate pathway might be of help.

https://pubmed.ncbi.nlm.nih.gov/26232225/

 

 

 

 


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Jcancom
(@jcancom)
Joined: 3 years ago
Posts: 434
01/08/2020 1:42 am  

This is another great metabolic masterpiece. Shut off MCT1, shut off the glucose supply to hypoxic cancer cells. It all begins to make intuitive sense. One could treat cancer as a Gedankenexperiment and only use the scientific literature to confirm what you have deduced.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582933/

 


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Jcancom
(@jcancom)
Joined: 3 years ago
Posts: 434
01/08/2020 7:27 pm  

This is extremely interesting! The attached file includes all human genes with their typical expression patterns in different tissues. Scientists have already used resources similar to this to discover that FerT is almost exclusively active only in cancer cells. The file below includes FerT (search for it in the second sheet of the spreadsheet.). However, this file suggests that FerT might be somewhat more widely expressed than exclusively in the testes. Wonder how accurate and complete this research is?

(I attached the full spreadsheet, probably could have simply included the url and saved space on the hard drive.)

This approach of looking for genes that are non-active in typical normal cells could have more widespread importance than I would have previously thought. As can be seen in the spreadsheet ( use the sort command for the different tissue columns), there are actually quite a fair number of genes that are (from current knowledge) not widely expressed elsewhere; for some reason the reproductive system appears to have many of these dedicated genes. What the e260 research with FerT found was that cancer sometimes can find a way to reactivate these genes for its advantage. If this did actually occur with some frequency in these largely inactive genes, then this might be a useful approach to consider more broadly in cancer management.  

https://www.broadinstitute.org/files/shared/metabolism/mitocarta/human.mitocarta2.0.html

 

 


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Jcancom
(@jcancom)
Joined: 3 years ago
Posts: 434
01/08/2020 8:56 pm  

The amino acids glycine/serine have attracted interest as their depletion has shown anti-cancer effects. In the figure below I am particularly attentive of GSH as it goes to the TCA and ROS. I think we can all remember how powerfully the 3-BP patient with melanoma responded when GSH was knocked down. LDH almost went to zero on the second treatment. GSH is a potent protector of the cell against ROS and "xeno-biotics" such as 3-BP. It seems to conjugate to any strange molecule that it encounters. However, once the cancer cell's GSH supply is exhausted, it is defenseless.

https://www.sciencedirect.com/science/article/pii/S0968000414000280

https://www.nature.com/articles/nature22056

 

Metabolic medicine have consistently been depicted on forum as nice, virtuous and modern approaches to managing cancer. The articles that I read about glycine/serine and then how this feeds into so called 1 carbon metabolism/folate cycle etc. noted that such presumed virtuousness might be somewhat illusory. Anti-folates were at the leading wave of cancer chemotherapy in the 1940s. Clearly disturbing some metabolic pathways can lead to side-effects and this is possibly why the pharma have avoided targeting even more centrally located pathways such as glycolysis.

 

http://cology4u.blogspot.com/2011/06/anti-cancer-drugs-i.html


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