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New cancer therapy holds potential to switch off major cancer types

princeton.edu

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Re: New cancer therapy holds potential to switch off major cancer types

#71

Post by marliechiller »

0x1062 wrote: post #62
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

You're challenging someone with 15 years experience studying this particular gene... by quoting Wikipedia?

That someone has skin in the game and a reason to manipulate other peoples understanding for his own gain though. Not saying he is, but I dont think the original comment was unjustified

Re: New cancer therapy holds potential to switch off major cancer types

#72

Post by majkinetor »

yazaddaruvala wrote: post #48
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

Disclaimer: I’m not in these fields but I am curious enough about how the mechanisms work at a high level that I feel confident about the rest of this post. Two things to keep in mind: 1. Biology has never selected genes to maximize longevity, only to maximize healthy breeding. There are very likely tons of genes that make sense as a growing child but are harmful at a later age, e.g. a post menopause/vasectomy adult…

> Biology has never selected genes to maximize longevity, only to maximize healthy breeding.

That is assumption which is hard to validate. There is a case for longevity as children with longer living dedicated parents in the context of abundant resources will out survive those that are ditched by their parents.

> Delete the notable gene or just make a point mutation to disable it.

The article say that effect is the same with deletion and drug in mice. Why would you delete the gene when you can temporally prevent its function ?

> Delete the notable gene or just make a point mutation to disable it. Treat/wait the cancer into remission.

Yet nobody did nothing remotely close in humans, even for stuff that looks like highly beneficial in all contexts such as GULO gene.

Re: New cancer therapy holds potential to switch off major cancer types

#73

Post by majkinetor »

tux3 wrote: post #17
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

Angiogenesis is going to be important in wound healing, I suppose, but compared to the current side effects of chemo this seems relatively minor. I agree that "no obvious side effects" seems excessive if you interpret that as the expected result in humans. Still, on paper this looks much more specific that anything we have.

Considering that people still get prescribed Thalidomide to limit angiogenesis as a cancer treatment, and we know about its side effects (lets ignore birth defects for now), I see no particular difference with this drug.

Re: New cancer therapy holds potential to switch off major cancer types

#74

Post by jdthedisciple »

0x1062 wrote: post #62
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

You're challenging someone with 15 years experience studying this particular gene... by quoting Wikipedia?

Ah the classic appeal-to-authority-fallacy ...

https://yourlogicalfallacyis.com/appeal-to-authority

Re: New cancer therapy holds potential to switch off major cancer types

#75

Post by mtts »

R0b0t1 wrote: post #46
bawolff wrote: post #22

Earlier quoted context omitted.

> It's not like evolution would select for something that is useless outside of helping cancer. Cancers often have genetic basis so in a sense evolution has already selected for it in some people or at least not selected against it. IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases.

> IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases. It gets even better: there is selective pressure for adults that have borne children to die so that their children can procreate. First noted in pea plants that send a chemical signal to kill themselves up from the pod, can be extended to animals in things like cancer rat…

Except that humans are not pea plants and having grandparents play an active role in child rearing significantly improves the survival odds for their grandchildren (who carry a quarter of their genes).

Re: New cancer therapy holds potential to switch off major cancer types

#76

Post by nindalf »

R0b0t1 wrote: post #46
bawolff wrote: post #22

Earlier quoted context omitted.

> It's not like evolution would select for something that is useless outside of helping cancer. Cancers often have genetic basis so in a sense evolution has already selected for it in some people or at least not selected against it. IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases.

> IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases. It gets even better: there is selective pressure for adults that have borne children to die so that their children can procreate. First noted in pea plants that send a chemical signal to kill themselves up from the pod, can be extended to animals in things like cancer rat…

Humans aren’t peas. Pea grandparents don’t help out in child rearing but human grandparents do. There is no indication that humans face selective pressure to die early.

Re: New cancer therapy holds potential to switch off major cancer types

#77

Post by donkeyacc »

bedobi wrote: post #18
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

I know nothing about biology, medicine or evolution, but I don't think that's how it works. Lots of people inherit and pass on all kinds of bad genes that do terrible things to them, even kill them. And for such people, switching them off would be better pretty much irrespective of any side effects. (to the degree there even are any side effects at all)

> I know nothing about biology, medicine or evolution, but

well, by all means, don't let that stop you

Re: New cancer therapy holds potential to switch off major cancer types

#78

Post by branko_d »

jdthedisciple wrote: post #74
0x1062 wrote: post #62

Earlier quoted context omitted.

You're challenging someone with 15 years experience studying this particular gene... by quoting Wikipedia?

Ah the classic appeal-to-authority-fallacy ... https://yourlogicalfallacyis.com/appeal-to-authority

I think it's important to distinguish the authority of expertise from the authority of power.

Re: New cancer therapy holds potential to switch off major cancer types

#79

Post by konschubert »

yazaddaruvala wrote: post #48
EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

Disclaimer: I’m not in these fields but I am curious enough about how the mechanisms work at a high level that I feel confident about the rest of this post. Two things to keep in mind: 1. Biology has never selected genes to maximize longevity, only to maximize healthy breeding. There are very likely tons of genes that make sense as a growing child but are harmful at a later age, e.g. a post menopause/vasectomy adult…

Also, evolution isn't "complete". It's not done optimising. And sometimes, some things evolve and there just isn't enough evolutionary pressure to remove stuff that does't hurt. Men have nipples.

Re: New cancer therapy holds potential to switch off major cancer types

#80

Post by nikita2206 »

EMM_386 wrote: post #14

> MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects I'm not fully buying that. If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer. I'd be curious…

I didn’t read the article fully but the parts of those two papers that are public and available to me (see Extended data Fig.4 comment at the bottom of the first paper), those do not talk about turning off a gene that encodes MTDH.

The paper is talking about a compound (two compound candidates) that inhibit binding of two proteins: AEG-1 (encoded by MTDH) and SND1, those compounds do that by binding to either AEG-1’s or SND1’s site where otherwise SND or AEG-1 would have bind, and they likely do this with stronger bond than SND1 and AEG1 would have had.

So in short, this compound does not leave you without some vital protein but disrupt formation of some bonds with SND1 protein.

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