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CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

innovativegenomics.org

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Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#151

Post by ben_w »

dylan604 wrote: post #144
ben_w wrote: post #64

Earlier quoted context omitted.

Usually it takes about a decade for most medical inventions to work their way through medical bureaucracy[0], so I'd say that 10 years ago we were at the stage of watching Matthew Broderick war-dialling with an acoustic coupler and reading Usborne Books telling us that criminals of the future would work from home, and today we're in the exciting early days of dialup, AltaVista, and GeoCities[1]. [0] The covid vaccine…

So according to your timeline, we're ~10 years from medical research becoming enshitified?

Depends where in the history of the web you count it as such. For me it was more like the late 2010s when that happened, so 20 years. And of course vanity surgery is already a thing, so it may have already happened to an extent with medicine?

10-20 years for an Alastair Reynolds' style Indoctrinal Virus? I hope not, but I can totally see it happening eventually.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#153

Post by TaupeRanger »

Asfand3099 wrote: post #140

What stands out to me is how cancer therapy keeps moving from broad destruction (chemo/radiation) toward increasingly precise identification of malignant cells. The challenge no longer seems to be "can we kill cancer cells?" but "can we reliably identify only cancer cells and reach all of them?" This paper looks like another step in that direction.

I'm not sure what this comment means - we could always kill cancer cells, and the challenge has always been "how can we ONLY kill the cancer?" We've been burning cancer, cutting cancer out, and drugging cancer cells for decades or centuries depending on the method. What is changing is not the type of challenge, but the precision of our tools - and even then, it remains to be seen if we actually can get the precision while improving the lives of the patients.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#154

Post by zevets »

himata4113 wrote: post #149
r58lf wrote: post #146

Earlier quoted context omitted.

It's not as great as you might think, despite all the stories you see like this one. That's because most of the stories are in cells (this one) or mice. The big success story, about 20 years old now, is testicular cancer. You can have metastatic testicular cancer with tumors all over your body (like Lance Armstrong had) and they can cure it. They use platinum based chemotherapy and it's not really well understood why…

I guess then a graph of deaths from disagnosed cancer at various stages would be just as awe inspiring. I'd settle for that as well.

https://www.cancer.org/content/dam/cancer-org/research/cance...

Page 2 has the figure. Getting people to not smoke has been the most effective treatment in our lifetime.

Public health is a really big deal, and RFK et al are a disaster for the nation.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#155

Post by rolph »

strbean wrote: post #84
MontyCarloHall wrote: post #70

The idea of using CRISPR/Cas to detect tumor-specific mutations that aren't necessarily oncogenic and then kill the cell is not a new one [0, 1, 2]. However, previous studies used Cas9, which just damages the DNA at the target site; this uses Cas12a2, which is far more destructive because it shreds the chromatin in the cell once activated by detecting the target sequence. As with any cancer treatment, it's likely the…

Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells? Like, it stops surfacing some cholesterol receptor because the drug is being delivered by LNPs that target that receptor, and now the cell is starved for cholesterol? I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could eff…

>would resistance also potentially cripple the cancer cells?this is the concept of genetic baggage, and metabolic budget.

there is only so much energy to a cell, and scant amounts to "waste" on preservation of something that is not used. in the long term, carrying unused properties are disadvantageous, and reduce reproductive output [replication]

the result is "unfettered" oncocytes outgrow those with baggage, and occlude access to resource. if there is no challange that reduces population of nonresistant cells, the resistance will be minimized and extinct in the face of large disparity of success.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#156

Post by tstactplsignore »

ordinaryradical wrote: post #32

CRISPR is an extremely overhyped approach which found a marketing engine via popular science. There is 1 FDA approved CRISPR therapy as compared to 7 for AAV and 7 for Lentivirus. Counting all viral vector therapies that have been approved, we’re sitting at 19 approved therapies versus 1 for CRISPR. I think CRISPR ideas in a lab are just an easy way into the mainstream press, but viral vector delivery is the real fut…

This comment doesn't understand why CRISPR is such a big deal in science. While Cas-as-a-therapeutic is easy for the public to understand, and therefore often emphasized in popular science, the primary use of CRISPR Cas systems is in modifying genes in the lab.

Tens of thousands of papers have made important scientific advances using it successfully and CRISPR-Cas methods are used routinely throughout almost all of biology.

This is like calling PCR "overhyped" because PCR-based infectious disease diagnostics are limited.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#157

Post by MontyCarloHall »

strbean wrote: post #137
MontyCarloHall wrote: post #89

Earlier quoted context omitted.

>Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells? Yes, if the LNP could be engineered to target an essential surface receptor, which is still a very tough problem. It would also not solve the issue of the payload successfully entering the cell but being subsequently degraded. >I've heard about drug resistance in bacteria leading to slower growth / reduced virulence.…

Interesting, thanks for the info! Another question: how does this approach compare to trying to repair the pathogenic variants in the cancer? I asked here about that approach recently and the response was mainly about delivery difficulties: https://news.ycombinator.com/item?id=48285386

Even with 100% delivery efficacy, editing efficacy is nowhere near 100%. CRISPR/Cas editors will reliably detect the target sequence but will not reliably edit it in order to repair the mutant allele, whereas CRISPR/Cas12a2 will activate and destroy chromatin ~100% of the time when it detects the target.

As is often the case, it's a lot easier to indiscriminately destroy than precisely (re)build.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#158

Post by himata4113 »

zevets wrote: post #154
himata4113 wrote: post #149

Earlier quoted context omitted.

I guess then a graph of deaths from disagnosed cancer at various stages would be just as awe inspiring. I'd settle for that as well.

https://www.cancer.org/content/dam/cancer-org/research/cance... Page 2 has the figure. Getting people to not smoke has been the most effective treatment in our lifetime. Public health is a really big deal, and RFK et al are a disaster for the nation.

Oh wow, not as impressive as I thought, but I guess we are looking at broad categories rather than specific types and variants. But overall the trend is down on ever cancer since around a decade ago. Was expecting a sharper drop around 1-2 decades ago, but things just take time when it comes to experimenting with human lives. Will be interesting to revisit this in another decade when a lot of the treatments finally leave the experimental stage.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#159

Post by jacinda »

r58lf wrote: post #146
himata4113 wrote: post #129

Does anyone know a website where I can see/read of how many cancers (and their variants) we've effectively solved, have drugs to negate their effects, have experimental drugs for and uncurable cancers? I think that graph would be awe inspiring looking at the past decade of advancements. What's more crazy is that we're slowly going from millenia, to decades, to likely years in the near future from being presented a bi…

It's not as great as you might think, despite all the stories you see like this one. That's because most of the stories are in cells (this one) or mice. The big success story, about 20 years old now, is testicular cancer. You can have metastatic testicular cancer with tumors all over your body (like Lance Armstrong had) and they can cure it. They use platinum based chemotherapy and it's not really well understood why…

Amen to childhood leukemia rates improving being awe-inspiring. I had a friend I rode the bus with around 2001 who was diagnosed with leukemia and didn't make it. They let us know over the PA system at school. I suspect these days she would have survived.
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