Submitted by BousWakebo t3_123ofc9 in Futurology
r0b0c0p316 t1_jdwq1gi wrote
Reply to comment by JackD4wkins in Scientists discover how cancer cells evade immune system by BousWakebo
We have lots of things that will destroy cancerous cells. The main problem is making sure they specifically target the cancer and not any normal tissue.
JackD4wkins t1_jdwq9d8 wrote
Doesn't seem to be a concern when we're using chemo and radiation as the current standard of care lol. Today, ~10% of all new cancers are linked to prior cancer treatments
r0b0c0p316 t1_jdwrms7 wrote
Many chemotherapy drugs are designed to inhibit or kill rapidly dividing cells which allow us to hit cancers with some specificity but other cell populations are also hit as a side effect. This is the reason why many people on chemo lose their hair; hair follicle cells are susceptible to the same chemo drugs.
Radiation is targeted by aiming a beam at the tumor. By using multiple beams that converge at the tumor site, we can ensure that surrounding tissue receives a lower more tolerable dose.
JackD4wkins t1_jdwsofu wrote
Chemo is so toxic that the people administering it cannot even touch it.... and don't get me started on radiation.
These treatments are brutal, carcinogenic in their own rights, and are not even necessarily curative. Crispr enzymes coded specifically to attack cancer DNA has been proven to not affect ANY healthy cells, while selectively annihilating cancer cells in vivo.
r0b0c0p316 t1_jdx3zwm wrote
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.
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
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.
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
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.
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
king5327 t1_jdyslcs wrote
Healthy and cancerous cells have almost exactly the same DNA. Minus a few mutations. CRISPR can target them, but might not necessarily be able to do anything useful at those locations.
CRISPR can't tell the difference between cells, it only targets specific sequences. Cancer can be caused by many different mutations, some of which won't cause it on its own. A bad target could lead to complications.
CRISPR has to work on all of the cells, otherwise the stragglers will start a new tumor.
Altogether, for CRISPR to work needs a safe target where the change will be effective and it has to wipe the floor with all of the cancer. Which means the patient needs to be lucky for it to even be a possibility, even if the success rate is high once administered.
(Source: mostly things I've read over the past decade and a half, I may be out of date)
JackD4wkins t1_jdyyu13 wrote
Crispr has been demonstrates to act at cancer causing mutation locations. Target selection is vital to success and require targeting multiple different mutations simultaneously.
Bad targeting has been rare and inconsequential in the context of current treatment side effects i.e. chemo and radiation.
Crispr can by used more than once to mop ip stragglers.
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