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CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
141–150 of 239 posts
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#142CRISPR 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…
I would guess you did not first write “CRISPR is an overhyped approach”, then after careful reflection decide, I don’t think that quite captures the intensity, better go with “extremely overhyped”.
The comparison is kind of a category error. One is a DNA editing technique and the others are deliver platforms. I recall the hype mostly being how revolutionary it could be, not comparing it on a timeline to specific technologies that are at different levels of the stack.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#143Earlier quoted context omitted.
> would cause the society to prioritize this over adtech? Private pharmaceutical R&D spending in the U.S. is around $100bn per year [1]. NIH spends another $50bn a year on biomedical research [2]. That eclipses total investments into adtech per se , which generously counted shouldn’t exceed $50 to 60bn. (And that only by counting like a third to a half of Google, Amazon, et cetera R&D and capital spending as adtech.)…
One of the primary challenges of drug and device economics is the long lead time between capital deployment and returns. One of the selling points of tech is speed to Market. Factors that would make it more attractive our lower interest rates, higher returns, or faster development. All of these are theoretically possible to adjust, but the last is most feasible to do in a tailor-made way through FDA review and approv…
Totally agree. I’m just pointing out that OP’s precondition is baseless: we do “prioritize this over adtech.”
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#144Earlier quoted context omitted.
So we're waiting for the Apple of the medical world to take a bunch of preexisting things to be applied together in a way that makes the whole much more valuable than the pieces. Or we need all of the individual lions to come together to make the Voltron?
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?
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#145Earlier quoted context omitted.
So we're waiting for the Apple of the medical world to take a bunch of preexisting things to be applied together in a way that makes the whole much more valuable than the pieces. Or we need all of the individual lions to come together to make the Voltron?
I think realistically we're waiting for someone in the top 10-20 richest people in the world to get cancer (or a close relative etc) who will then throw billions at research to try and fix the problem.
We spend upwards of $15B a year globally on cancer research. About half of that is funded by government and charities, half by pharmaceutical companies.
If spending billions was the main trick, we’d know it already.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#146Does 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 it works for testicular cancer, but not others.
The story with childhood leukemias is similar. They figured out how to combine a bunch of chemotherapy to get the cure rate up pretty high. Leukemia in a child used to be (1990s) 90% fatal, it's like 10% now.
Besides those, most of the advances in the past few decades come from early detection/ surgery or just prevention (stop smoking).
There is some hope though. When people first started studying cancers at the molecular level, one of the first things they noticed was how often a gene called Ras was mutated in different cancers. It turns out that designing a drug for Ras was really hard, but it finally got done, it's called daraxonrasib. They just released phase III human trials with this drug in pancreatic cancer a week or two ago and it destroyed the standard of care (Chemotherapy), but that is saying people who were dying in 1-2 months were still alive after 5-6 months.
The former senator Ben Sasse was diagnosed with metastatic pancreatic cancer last December. Historically, that's like 5% survival rate for 5 years. He is on daraxonrasib. We will see how it works out.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#147Earlier quoted context omitted.
This would shorten the timeframe for cells to mutate and acquire resistance mechanisms, but would not address the issue of cells with preexisting (epi)genetic resistance mechanisms that would then be promptly selected for.
Yes, and if you shorten the timeframe enough, there's a chance that it can clear all the cancerous cells. You also ideally would use multiple variations of the therapy to further reduce the chance of a pre-existing escape mutation. That's how we deal with HIV. No single HIV therapy (so far) is effective enough to suppress the virus all by itself, but a combination of them provides a barrier that is too high for mutat…
Agreed. Assuming it's ultimately proven to work in vivo, I think the endgame of this therapy is multiple guides targeting multiple mutations along with multiple delivery mechanisms (a formulation-diverse cocktail of LNPs + eVLPs [0]?). Sure, tech like [0] is futuristic and fanciful, but so is the tech of the OP, and both will probably reach in vivo maturity around the same time.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#148The 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…
turn the stick around and grasp the other end.
evolution isnt about generating a response to a challenge, its about differential success.
those cells [oncocytes] that have properties conferring resistance carry it as un-utilized baggage, those without said properties make a living without that fetter.
the selective factor comes into play when payloaded LNP [in this case] facillitates destruction of "nonresistant" oncocytes and spare the "resistant"
the resistance is not generated in response to the challenge, it is already present, and confers survivorship in the face of the administration of the drug.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#149Does 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…
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.
Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
#150Earlier quoted context omitted.
I think realistically we're waiting for someone in the top 10-20 richest people in the world to get cancer (or a close relative etc) who will then throw billions at research to try and fix the problem.
We spend upwards of $15B a year globally on cancer research. About half of that is funded by government and charities, half by pharmaceutical companies. If spending billions was the main trick, we’d know it already.
Do we actually spend it, or do we raise that much money while only a fraction of it goes to research?