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Viri and the combat of cancer...


RyanJ

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After recently reading an article in a science magazine about how they are trying to use viri to fight things like colds I got thinking.

The reason this is so hard is that the virus mutates - I already know, again form the magazine that viruses are being tested in the treating of cancers but would it be possible to use the viruses mutations as a weapon too?

 

What I mean is this: A virus can mutate but so too can a cancer, could you engineer a virus that mutates "in sync" with the cancer cells it was designed to destroy? That way the effect would make the cancer mutations useless because the virus would simple mutate in a way that makes the mutation useless.

 

 

Anyone have any comments on that or if it would be possible?

 

Cheers,

 

Ryan Jones

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It's pretty hard to make something mutate in the same way, unless it does the same things and has the same structures.

 

Anyways, say the cancer cells mutate so that they lose the receptor that the virus uses to get in. The virus mutates in the same way. That doesn't mean it can get in now. It has mutated in the same way, but the original mutation still negated its effect.

 

And it's viruses, not viri.

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It's pretty hard to make something mutate in the same way' date=' unless it does the same things and has the same structures.

 

Anyways, say the cancer cells mutate so that they lose the receptor that the virus uses to get in. The virus mutates in the same way. That doesn't mean it can get in now. It has mutated in the same way, but the original mutation still negated its effect.[/quote']

 

Hmm.. but there must be some way to make it mutate so that even if the cancer cell mutates it too would still have the ability to destroy it. Sort of like an adaptive mutation?

 

Cheers,

 

Ryan Jones

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If that was possible' date=' I think it would be bloody useful.

 

Unfortunately I don't think it is. You just can't make a virus that's "smart" enough to think "gee, I can't get in through that receptor, so why not try going through this one over here?"[/quote']

 

I'm not saying anything as complex as that... lets start with are cancer mutations just random? I'm guessing they are probably not random too much of an extent in that case there is adatability room for a virus working along those lines if you get what I mean, the more random the less chance of the adaption working.

 

Cheers,

 

Ryan Jones

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Of course they aren't random. The cancer cells that mutate so that the virus can't get into them survive. The virus has to wait until it mutates to that it can get into the cancer cell. There is no way for it to say "the cancer cell has mutated, I should mutate to counter that" except through several generations of mutations to see what works.

 

edit: what ecoli said

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I can't see how the virus would be able to "keep up" with the cancer cell. There is no real way to predict how the cancer cell is going to change, so how does your virus know when to change and what to chagne.

 

 

Thats the point, it can't in that way!

 

I'm thinking that if, like a mathamatical sequence, you could find some way to make the vuruses adapt based on the way it mutates, according to an inverse system, then you could make it adapt bases on the inversion of how the cancer cell mutated allowing it mutate with it.

 

Another problem as you said was the keeping up part, assuming again that the cancer cells donot just mutate at a random time there should again be a way to overcome this after all our bodies do use time to regulate some things.

 

A better idea may be to make a semi-adaptive one, after it hijacks the host cell it intergrates part of the DNA into its self allowing it to attempt to preduict how it would adapt. Though if this virus managed to attack other cells it would then be all but unstoppable due to its adapability... There could be no immunity to this type of virus.

 

Cheers,

 

Ryan Jones

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I'm thinking that if, like a mathamatical sequence, you could find some way to make the vuruses adapt based on the way it mutates, according to an inverse system, then you could make it adapt bases on the inversion of how the cancer cell mutated allowing it mutate with it.

The problem is that viruses don't understand mathematics. You'd have to find a way to make it beneficial to them to mutate in that way (and remember, they'd already have to be in a host cell for them to be reproducing).

 

Another problem as you said was the keeping up part, assuming again that the cancer cells donot just mutate at a random time there should again be a way to overcome this after all our bodies do use time to regulate some things.

They mutate when they reproduce. With viruses, the proteins controlling their reproduction go bonkers.

 

A better idea may be to make a semi-adaptive one, after it hijacks the host cell it intergrates part of the DNA into its self allowing it to attempt to preduict how it would adapt. Though if this virus managed to attack other cells it would then be all but unstoppable due to its adapability... There could be no immunity to this type of virus.

Erm. Once the virus gets inside of the host, it doesn't matter if the host mutates or anything--the virus is already inside. And you can't predict mutations. It's a matter of if the RNA screws up or doesn't screw up.

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The problem is that viruses don't understand mathematics. You'd have to find a way to make it beneficial to them to mutate in that way (and remember, they'd already have to be in a host cell for them to be reproducing)

 

*Hits head against a table* I know that (I don't understand mathematics either so we have something alike there)... I said like. Is, somehow, you could make a virus so it could adapt in a way that was like it was following a pre-defined system of mutations.

 

They mutate when they reproduce. With viruses' date=' the proteins controlling their reproduction go bonkers.

[/quote']

 

Thats perfect, if a virus is already in the cell it has no problems and not only that but its "offspring" culd then be easily made to attack those types of cells again later.

 

Erm. Once the virus gets inside of the host' date=' it doesn't matter if the host mutates or anything--the virus is already inside. And you can't predict mutations. It's a matter of if the RNA screws up or doesn't screw up.

[/quote']

 

But surly some parts of the DNA are more likley to mutate than others? And yet agin here we go with the viruses not understanding probabilities... I know - what if they were sort of pre-programmed to "snip" certain pats of the DNA.

 

I know, we are nott anywhere near this level of technology yet but lets assume we are some advanced civilisation for now :)

 

Anyone have any other ideas about how this may be done (Hypothetically)?

 

Cheers,

 

Ryan Jones

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*Hits head against a table* I know that (I don't understand mathematics either so we have something alike there)... I said like. Is, somehow, you could make a virus so it could adapt in a way that was like it was following a pre-defined system of mutations.

The point is that mutations are simply failures of RNA to match the right pyrimidines and purines together during transcription. They're not programmable.

 

But surly some parts of the DNA are more likley to mutate than others? And yet agin here we go with the viruses not understanding probabilities... I know - what if they were sort of pre-programmed to "snip" certain pats of the DNA.

That would be difficult to manage. And the point is that they can all mutate equally, but a lot of mutations result in the cell dying or not reproducing.

 

The best thing to do would be to make a virus that exploits a part of a cell that changes slowly, such as something that is very difficult to change and get to work right. Certain parts of a cell, like receptors, can change, leaving the cell fully functional, but other parts would have to change in exactly the right way for them to still work. Target the latter, and it works.

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The best thing to do would be to make a virus that exploits a part of a cell that changes slowly' date=' such as something that is very difficult to change and get to work right. Certain parts of a cell, like receptors, can change, leaving the cell fully functional, but other parts would have to change in exactly the right way for them to still work. Target the latter, and it works.[/quote']

 

Thats a good one, I like it. If you can keep a copy of a virus inside a cell it can keep altering he DNA, making the receptors stay the same, if it cna do this then the immune system should be able to adapt too then and kill them.

 

That sound right too you?

 

Cheers,

 

Ryan Jones

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Ryan, I don't know if this is what your looking for, but I thought I would post it just in case. As a women with ovarian issues, I've been watching for the latest in stealth virus research and ovarian cancers. I can't find the other article I had, but researchers have also found an form of echovirus that specifically targets SCLC (small cell lung cancers) I believe.

 

 

Echovirus type 1 effective in ovarian cancer model

 

Reuters Health

Posting Date: June 23, 2005

 

Last Updated: 2005-06-23 12:31:49 -0400 (Reuters Health)

 

NEW YORK (Reuters Health) - Laboratory studies conducted in Australia provide an "important proof of principle" that wild-type echovirus type 1 (EV1) may be an effective oncolytic agent for human ovarian cancer, according to a report in the June 10th issue of the International Journal of Cancer.

 

While screening human enteroviruses for their oncolytic capacity, Dr. Darren R. Shafren from the University of Newcastle in New South Wales and colleagues found that EV1 displayed a "high level of tropism" for human ovarian cancer cells, an observation that led to the team's current work.

 

They observed that EV1 lytically infected all eight human ovarian cancer cell lines tested, but did not infect a normal ovarian surface epithelial cell line or human peripheral blood mononuclear cells.

 

"EV1 challenge was equally effective in the oncolysis of human ovarian cancer cells whether in monolayer or spheroidal environments," they note.

 

In SCID mice bearing ovarian subcutaneous xenografts, direct intratumoral inoculation of EV1 rapidly reduced the tumor burden not only of the injected tumor but also of tumors distant to the injection site.

 

Intraperitoneal administration of EV1 was also effective against "widespread ovarian xenografts in the peritoneal cavity in the mouse ascites model of human ovarian cancer."

 

Preliminary (unpublished) evidence suggests that EV1-induced cell cytolysis is largely mediated by cellular necrosis and not by induction of apoptosis, the team notes.

 

These findings, the authors say, suggest that the "relatively noninvasive EV1 therapy may be viewed as an attractive alternative to current treatment regimens that involve surgical debulking followed by combination chemotherapy." EV1 therapy may also be a useful adjuvant therapy following tumor-debulking to target and destroy neoplastic cells released during surgery.

 

Int J Cancer 2005;115:320-328.

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What I mean is this: A virus can mutate but so too can a cancer' date=' could you engineer a virus that mutates "in sync" with the cancer cells it was designed to destroy? That way the effect would make the cancer mutations useless because the virus would simple mutate in a way that makes the mutation useless.

 

 

Anyone have any comments on that or if it would be possible?

 

Cheers,

 

Ryan Jones[/quote']

 

Ok first, you have to understand that mutation rates are directly related to generation times. Viruses have a much faster replication cycle then any eurkaryotic cell ever could hope (yes, even much significantly faster then cancer cells) so therefore it is very unlikeley that a cancer cell could 'out mutate a virus'.

 

Second, cancer cells always arise from normal human cells. Virsues used for oncolytic purposes (ie to target and kill cancer cells) target receptors that are present on normal cells, however they are manipulated by scienctists to have specific qualities that only allows them to grow in the altered cellular enviroment that occurs in cancer cells. In order for a cancer cell to mutate its cellular receptor to prevent viral entry that would require at least some sort of DNA or RNA synthesis. However, oncolytic viruses kill cancer cells. So even if a cancer cell managed to completley delete its viral receptor (or change it enough so a virus couldn't recognize it) this would have to happen probably over multiple generations, assuming it could even happen at all. But viruses that target cancer cells are oncolytic, meaning that the cancer cell would die before it could even respond to this selective pressure.

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