6 replies to this topic

[ihatesnow]

http://www.broadinst...e.org/news/7706

[Logic]

In a landmark study, researchers from the Broad Institute and Massachusetts General Hospital reveal a completely new biological mechanism that underlies cancer. By studying brain tumors that carry mutations in the isocitrate dehydrogenase (IDH) genes, the team uncovered some unusual changes in the instructions for how the genome folds up on itself. Those changes target key parts of the genome, called insulators, which physically prevent genes in one region from interacting with the control switches and genes that lie in neighboring regions. When these insulators run amok in IDH-mutant tumors, they allow a potent growth factor gene to fall under the control of an always-on gene switch, forming a powerful, cancer-promoting combination. The findings, which point to a general process that likely also drives other forms of cancer, appear in the December 23rd advance online issue of the journal Nature...

 

 

PDGFRA and FIP1L1, which are normally confined to separate loop

domains (A) rarely interact, but can become closely associated in
IDH-mutant tumors (B). Image by Lauren Solomon, Broad Communications

 

...Just as the loops of a tied shoelace come together at a central knot, two insulators in the genome bind to one another, forming a loop. These insulators join together through the action of multiple proteins, which bind to specific regions of the genome, called CTCF sites...

 

...IDH encodes an enzyme that, when mutated, produces a toxic metabolite that interferes with a variety of different proteins....

 

Note that Nilotinib get rid of misfolded proteins in the brain, although i dont know if this includes the above.

http://www.longecity...ative-diseases/

 

Edited by Logic, 25 December 2015 - 07:04 AM.

[corb]

Note that Nilotinib get rid of misfolded proteins in the brain, although i dont know if this includes the above.

 

DNA folding is a completely different mechanism from protein folding.

 

Here there is a popular Numberphile video on the topic https://youtu.be/AxxnziuL408

[Logic]

 

Note that Nilotinib get rid of misfolded proteins in the brain, although i dont know if this includes the above.

 

DNA folding is a completely different mechanism from protein folding.

 

Here there is a popular Numberphile video on the topic https://youtu.be/AxxnziuL408

 

 

 

 

"...IDH encodes an enzyme that, when mutated, produces a toxic metabolite that interferes with a variety of different proteins..."

Is what I was alluding to in 'the above' Corb.  

I would have thought you 'knew me' better than that by now?!

 

[corb]

Ok now I get what you meant.
Nilotinib like most drugs it's interaction with every protein and enzyme has not been investigated so this might be one mechanism through which it operates.  But it is a cancer drug, so we pretty much know it's efficacy with cancers. Of course finding new drug targets is always helpful. Or it would be in a perfect world where Big Pharma doesn't exist.

 

Anyway when I read this article I was thinking about targeting the DNA maintenance systems that deals with DNA folding instead. It's more general than targeting any specific metabolite which for different cancers are probably different anyway.

[Logic]

Ok now I get what you meant.
Nilotinib like most drugs it's interaction with every protein and enzyme has not been investigated so this might be one mechanism through which it operates.  But it is a cancer drug, so we pretty much know it's efficacy with cancers. Of course finding new drug targets is always helpful. Or it would be in a perfect world where Big Pharma doesn't exist.

 

Anyway when I read this article I was thinking about targeting the DNA maintenance systems that deals with DNA folding instead. It's more general than targeting any specific metabolite which for different cancers are probably different anyway.

 

Cool.  

So any ideas on 'targeting the DNA maintenance systems'?

[corb]

 

Ok now I get what you meant.
Nilotinib like most drugs it's interaction with every protein and enzyme has not been investigated so this might be one mechanism through which it operates.  But it is a cancer drug, so we pretty much know it's efficacy with cancers. Of course finding new drug targets is always helpful. Or it would be in a perfect world where Big Pharma doesn't exist.

 

Anyway when I read this article I was thinking about targeting the DNA maintenance systems that deals with DNA folding instead. It's more general than targeting any specific metabolite which for different cancers are probably different anyway.

 

Cool.  

So any ideas on 'targeting the DNA maintenance systems'?

 

 

There are known enzymes which take care of DNA folding, coiling and knotting and so on - I don't know them, I'm not a geneticist. So, the easiest way to see if this is an important mechanism in cancer formation is to simply overxpress these maintenance genes in an animal. If the modified batch gets less cancers than a wild type batch, then this is important and it would be beneficial to invest money and human resources into.
You get a potential prophylactic treatment and experimental proof out of a single experiment in the best case scenario.

 

It's probably not that simple in reality of course. But you generally get my idea.