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r0b0c0p316 t1_jdx3zwm wrote

Reply to comment by JackD4wkins in Scientists discover how cancer cells evade immune system by BousWakebo

I agree that chemo and radiation are not great options for fighting cancer. The fact that they have off-target effects is a problem, and that's my point; that it's difficult to only target the cancer.

How do you get CRISPR delivered to tumorigenic cells without targeting normal healthy tissue? Targeting anything to specifically hit cancer is tough because cancer presents so similarly to healthy tissue. If you have any papers that discuss this cancer-specific CRISPR targeting I would love to read them because I haven't seen anything about it that's unique to the CRISPR system.

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JackD4wkins t1_jdxdxlh wrote

You can easily code crispr to target specific strings of DNA. Just take a sample of a patients cancer, analyze which parts of DNA are driving that specific cancer, code your crispr enzyme accordingly, pack it into a virus, and away you go... its really not complicated. Even if the virus infects a healthy cell, the crispr enzyme is specific to cancer DNA and has no effect on healthy dna. The amount of off-target effect is negligible compared to current treatments i.e. chemo and radiation.

The system combines crispr with cancer bioinformatic analysis. Check out CINDELA in sourth korea

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r0b0c0p316 t1_jdxjxyc wrote

I found this PNAS paper on CINDELA which is a pretty cool proof of concept but it's still far from being an effective treatment (just like the results of the research from the OP). Their mouse experiments were compelling but a lack of comparison between tumor cells vs healthy cells from the same mouse or patient, plus the short time-frame where they administer their sgRNAs means that we can't know for sure what any off-target effects there might be. Also, since it can take as few as 6 driver mutations to generate a cancerous cell, it may not be possible to find 20+ unique indels specific to the cancer but not found in healthy cells.

It could be a promising treatment in combination with other therapies, but there's still a lot more work to be done before its ready for human trials.

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JackD4wkins t1_jdxkg2x wrote

Once a cell becomes cancerous, the rapid division facilitates further mutation, providing more targets.

Crispr has been shown to have very few off-target indels when coded correctly.

Nevermind other treatments - if we can get this scaled, this may be the silver bullet we stopped believing in

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r0b0c0p316 t1_jdxmclb wrote

> Once a cell becomes cancerous, the rapid division facilitates further mutation, providing more targets.

That's a fair point, but this also means that tumors have significant heterogeneity, so it can be difficult to find sufficient indels to target. I like your enthusiasm, but this research is still a long ways off from being a 'silver bullet'. Even the paper's authors discuss using it in combination with other treatments.

I'm not saying it won't work; I'm just saying it'll take a lot more funding and research to find out and it's not as simple as you might think.

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JackD4wkins t1_jdxt1rw wrote

A man can dream haha. I'm partial to multiple rounds of treatment personally. We ID the mutations to target, rip up those cancer cells, then target the remaining ones with different mutations. No chemo/ radiation side effects. It will not be a one-and-done. Will require multiple rounds to take down all of them. The goal is to avoid other treatment modalities completely to avoid their horrific side effects

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