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New cancer therapy holds potential to switch off major cancer types

Author: MKais

Score: 146

Comments: 18

Date: 2021-11-30 22:15:52

Web Link

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nick__m wrote at 2021-11-30 23:57:06:

PCLX-001 is similar drug in clinical trial that target cancerous cells but spares the healthy one, it's not the same target as the one in the article but I think (I'm not a biologist) that it's a similar mechanism. They even have a test to know beforehand if it's going to be effective in a particular cancer. It's developed by a company named Pacylex.

Here's the link to the clinical trial

https://clinicaltrials.gov/ct2/show/NCT04836195?term=pclx-00...

Edit: removed a duplicated word

pazimzadeh wrote at 2021-11-30 23:17:48:

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

EMM_386 wrote at 2021-12-01 00:35:03:

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 what the side effects are in humans. How can it be claimed that it can be eliminated with "no obvious side effects" when they are still years away from human trials?

https://en.wikipedia.org/wiki/MTDH

tux3 wrote at 2021-12-01 01:35:41:

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.

majkinetor wrote at 2021-12-01 01:25:36:

No obvious side effects in mice with knockout gene and using the drug.

The drug doesn't disable the gene but make the protein unable to do its function by preventing the binding with another protein. If it can make cancer chronic disease, any side effects it may have will probably be less important then death.

bedobi wrote at 2021-12-01 01:36:41:

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)

a9h74j wrote at 2021-11-30 23:26:41:

“You can’t find a drug target better than this: MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects,” said Kang.

alexk307 wrote at 2021-12-01 01:39:06:

Fascinating that they have to physically screen individual molecules one at a time to see if they can bind with a specific protein. Even at a Princeton lab, it took years. Are there other institutions/companies working in this space?

nielsbot wrote at 2021-11-30 23:33:38:

"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".

csdvrx wrote at 2021-11-30 23:44:32:

Actually, we can: I think we already have working gene therapy for several diseases.

Just look at the current list on wikipedia:

https://en.wikipedia.org/wiki/Gene_therapy#Treatment_of_gene...

moneywoes wrote at 2021-12-01 01:01:24:

As someone with some genetic diseases, it’s feels unfortunate to be born too early

thornjm wrote at 2021-11-30 23:46:55:

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.

The_rationalist wrote at 2021-11-30 23:43:11:

Epigenetics are very easy to alter with peptides

NKosmatos wrote at 2021-11-30 23:33:24:

Nicely written, well explained and let’s hope that the MTDH will help in suppressing cancer. Not yet available, but their hard work will soon pay out.

“I hope we’ll be ready for clinical trials in human patients in two to three years,”

fernly wrote at 2021-11-30 23:32:16:

So what is, or are, the "small-molecule inhibitors"? (I don't have access to the full texts of the papers.)

Also, what makes them confident these inhibitors "suppress breast cancer progression and metastasis"? Does this mean only in the mouse model? Because the original article says "will be ready for human trials in a few years".

tux3 wrote at 2021-12-01 01:48:40:

A small molecule is exactly what it says on the tin: small compounds. Small enough that they can pass through cell membranes.

Inhibitors block some biological pathway, which in general could be any number of things.

In this case the drug blocks a specific protein that we believe cancer cells specifically need, meaning the cancer cells might fail faster than the rest of your body if we inhibit it.

wetpaws wrote at 2021-12-01 00:25:02:

ctrl+f >in mice

timbit42 wrote at 2021-12-01 00:32:12:

...and human tissue.

FundementalBrit wrote at 2021-11-30 23:50:41:

The Chinese military are spending vast vast sums on gene therapy.

They call it precision medicine.