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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

#81

Post by carlmr »

nindalf wrote: post #76
R0b0t1 wrote: post #46

Earlier quoted context omitted.

> 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.

>There is no indication that humans face selective pressure to die early.

While I do agree that pea plants are different, human grandparents may help in child rearing, but they may also consume time and energy for care.

We're social animals that would not kill our own grandparents for having more food/time available. But nature might find it's useful for procreation if they don't live too long.

Elderly care is a huge time/energy sink. And longevity makes the input/output unfavorable in a lot of cases.

If you're in an environment like our ancestors where food was most of the time scarce, then that adds weight to this equation.

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

#82

Post by dorkwood »

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

From the link you posted:

> It's important to note that this fallacy should not be used to dismiss the claims of experts, or scientific consensus. Appeals to authority are not valid arguments, but nor is it reasonable to disregard the claims of experts who have a demonstrated depth of knowledge unless one has a similar level of understanding and/or access to empirical evidence.

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

#83

Post by fasteo »

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…

>>> 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 does not need the genes to create gametes but those same genes may be causing cancerous issues for some.

This is being debated, in the sense that there is a relationship between longevity and breeding. How ? For a human to be able to have kids every 2-3 years - instead of 6-7 in apes - older individuals have to be healthy enough to bring a calorie surplus to the mothers.

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

#84

Post by jdthedisciple »

dorkwood wrote: post #82
jdthedisciple wrote: post #74

Earlier quoted context omitted.

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

From the link you posted: > It's important to note that this fallacy should not be used to dismiss the claims of experts, or scientific consensus. Appeals to authority are not valid arguments, but nor is it reasonable to disregard the claims of experts who have a demonstrated depth of knowledge unless one has a similar level of understanding and/or access to empirical evidence.

At no point have I dismissed any expert.

Thanks for the quote tho, whats your point?

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

#85

Post by SubiculumCode »

marliechiller wrote: post #71
0x1062 wrote: post #62

Earlier quoted context omitted.

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

You acting like posters on HN don't have skin in the game as they try to appear smart in front of their peers.

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

#86

Post by stanrivers »

sharkweek wrote: post #60
01100011 wrote: post #57

Earlier quoted context omitted.

Yeah my friend has been doing that for about half as long. It still sucks. Some of the modern, immune-based therapies don't make your hair fall out, but they still can wreck your digestive tract, thyroid, and adrenals(in my friend's case, permanently). There are surgeries as well, and getting slowly hacked up as they chase tumor after tumor isn't fun. Still though, it's a better time to have cancer than ever I suppos…

I’m sorry your friend is in a similar position. There was one treatment that they were going to trial my friend on that would give him another expected extension but basically make his digestive tract stop working so he’d be pooping out of a tube into a bag the rest of his life but he declined, said it just wasn’t worth it. There have been a couple times that’s been the call he’s made and I appreciate why.

Good luck to your friend - sometimes it is not worth it, but the chances he has been taking and the suffering he has been going through in those trials where it is worth it is hopefully helping others in the future with the same disease.

Cancer sucks; why it is so hard for us to beat is so frustrating. need more research focused on this.

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

#87

Post by junon »

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

This isn't an appeal to authority, though. Also note there's a fallacy on there about using fallacies to discredit someone.

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

#88

Post by mnw21cam »

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…

The MTDH gene clearly has some utility in the human body. We know that because natural human knockouts are under-represented in the population. The Gnomad project has sequenced very many people's DNA, and they have been able to work out a formula for how many loss-of-function mutations they would expect to see in a gene (which mainly depends on the size of the gene). For the MTDH gene [0] they would expect to see on average 30.5 LoF mutations, but they only actually see 7. This is reasonably strong evidence that knockouts of this gene are selected against - that is, having two working copies of this gene conveys some advantage of some kind.

Knocking out the gene and gaining protection from cancer is likely a bigger advantage than whatever you lose, especially if you currently have cancer. Also, the proposed drug doesn't knock out the gene - it just prevents the protein from performing one of its interactions. Side effects are likely to take a while to work out, but if they're milder than the side effects of chemotherapy (which isn't hard) then that's a win.

The other thing I would like to point out is that humans and mice differ. It looks like most of the work they have done so far has been in mice. Knockout of this gene in mice doesn't seem to cause any ill effects. Working out whether the same is true in humans is a long and very careful process.

[0] https://gnomad.broadinstitute.org/gene/ENSG00000147649?datas...

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

#89

Post by koheripbal »

majkinetor wrote: post #72
yazaddaruvala wrote: post #48

Earlier quoted context omitted.

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 s…

I agree with your sentiment, but this condition...

> in the context of abundant resources

...has only been true for a tiny number of generations and so likely has not had a large evolutionary influence.

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

#90

Post by koheripbal »

konschubert wrote: post #79
yazaddaruvala wrote: post #48

Earlier quoted context omitted.

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.

Cancer definitely hurts.
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