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New cancer therapy holds potential to switch off major cancer types

princeton.edu

21–30 of 111 posts

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

#21
What takes years to develop for the human trials to start?

Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first?

There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.

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

#22
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…

> 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.

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

#23
post #18
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)

It’s one thing for a “bad” gene to stick around for a few generations or even spread through a species. It’s wildly different for a “bad” gene to be shared by species who’s common ancestor was 60+ million years ago. On that timescale anything conserved is doing something useful.

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

#24

Here is the research: Small-molecule inhibitors that disrupt the MTDH–SND1 complex suppress breast cancer progression and metastasis https://www.nature.com/articles/s43018-021-00279-5 Pharmacological disruption of the MTDH–SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer https://www.nature.com/articles/s43018-021-00280-y

Metastatic research really needs more funding. It's the true killing mechanism of cancer, and when this can be controlled, metastatic cancer can be classified as a chronic condition, not a terminal one.

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

#25

What takes years to develop for the human trials to start? Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first? There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.

Acquiring endless regulatory approvals.

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

#26
post #9
post #6

"Because while it’s important to show that mice born without MTDH are resistant to cancer, that doesn’t help patients, whose genes can’t be rewritten ." ...yet Wonder if we'll look back at this and think "how quaint".

Neo: “Are you trying to tell me that I can alter DNA?” Morpheus: “no Neo, I’m trying to tell you that when you’re ready you won’t have to” Altering the DNA is unnecessary if you can control the expression of genes or add additional genetic material later in the DNA->RNA->protein process. mRNA vaccines are already a great example of this. Another example might be the cystic fibrosis therapy Trikafta.

octopuses and their relatives—the cephalopods—practice a type of genetic alteration called RNA editing that’s very rare in the rest of the animal kingdom. They use it to fine-tune the information encoded by their genes without altering the genes themselves. And they do so extensively, to a far greater degree than any other animal group.

https://www.theatlantic.com/science/archive/2017/04/octopuse...

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

#27

What takes years to develop for the human trials to start? Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first? There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.

Acquiring endless regulatory approvals.

I wonder how much of our regulation around medicine is wasteful, vs regulation that came about in response to some sort of malfeasance.

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

#28
post #9
post #6

"Because while it’s important to show that mice born without MTDH are resistant to cancer, that doesn’t help patients, whose genes can’t be rewritten ." ...yet Wonder if we'll look back at this and think "how quaint".

Neo: “Are you trying to tell me that I can alter DNA?” Morpheus: “no Neo, I’m trying to tell you that when you’re ready you won’t have to” Altering the DNA is unnecessary if you can control the expression of genes or add additional genetic material later in the DNA->RNA->protein process. mRNA vaccines are already a great example of this. Another example might be the cystic fibrosis therapy Trikafta.

Disclaimer: I’m not a scientist, but I want to be.

For things like cancer cells which from a cell surface perspective, can look a lot like healthy cells, I don’t know how one only modifies DNA/RNA expression in only cancer cells. It would have to be all cells with maybe some cellular diagnosis logic in the DNA/RNA itself. Even then cancer evolves. It would have to done multiple times with something like cell descendents information.

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

#29

What takes years to develop for the human trials to start? Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first? There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.

From the article:

"yet it doesn’t seem to be important for normal development"

Gene space is huge. My cancer is cured, but now I'm dying of mange. So that's why that mouse kept licking itself. Big ask for someone else. They have trouble getting blood thinners, statins and beta blockers right. And there's no genetics there. It's stuff people ate out in the woods for hundreds of thousands of years.

> There are so many people close to dying in cancer finding volunteers for a Phase 1 test should be easy

I take the opposite approach. These people have few days left. It's a time to make things nice. It can get much worse quick. Cancer, which can be managed, is nowhere near as bad as it can get.

Disease tends to hit all at once. It's really just dying. Cancer, strokes, heart attacks and infections all tend to gang up at once. The trial will kill these people no doubt. If you have a ticket out of the hospital, take it! Don't squander it trying to wash mud.

Also the patient pays a lot for clinical trials. Hundreds of thousands of dollars.

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

#30
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…

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