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 biological problem and achieving the next milestone in solving it. We might have "AI", but we also have brilliant minds right now that are speeding up development to a pace that would be unimaginable just few years ago.
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.
I wouldn't understate advances in Melanoma treatment. Immunotherapies have absolutely changed the game in that space. It's not a curable cancer (few are) but it's far more treatable.
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.
That's understating the progress by a lot - many cancers are a lot more survivable now than previously with better chemo/radio/surgery + immunotherapies + car-t etc etc
There are lots of other success stories too. For example there is a reason why Keytruda is the most valuable medicine globally -- it does amazing things against melanoma and lung cancer
They are starting to ship this out across the country. My uncle has pancreatic cancer and is hoping to get a shipment in the next two months. Apparently you discontinue chemo while on it because it’s so unnecessary at that point.
It's difficult to do that because we don't even really know how many cancers there are.
Cancer is best understood as a family of tens of thousands of diseases. They're a whole range of different genetic changes that can happen which result in similar categories of symptoms and consequences. They can also be incredibly complex, such as being the result of hundreds of stacking genetic defects acquired over a lifetime. There can be a thousand varieties of one specific type of lung cancer, and they might all react differently. Some of our solutions might work on a lot of them, but others might only work on a handful. And we're at the beginning of figuring all this out.
CRISPR may eventually allow us to genetically profile a cancer and design highly targeted medications to cure them, but we don't know yet how well it will work. It may only work on a portion of them. It may have worse outcomes than chemotherapy or radiation. It's nice to think that we're going to find a magic solution to the entire problem, but things almost never work that way. I think we're going to be able to resolve a wide range of issues, but I don't think it will really cure cancer as a whole.
at the simplest level, the particular gene, and particular perturberance, sets the "type" of cancer.
there will most often be additional genetic abnormalities giving nuance to the character of the oncotype.
the tumour is originated from a cell type of specific differentiation, and developmental potency, further widening the pool of possible cancer type.
immunotype of cancer also sets the relationship between cancer and the body.
the cells of the body are setup for a functional death and replacement so when you try to rescue a particular cell [or cohort] you are fighting against how the grand scheme of tissue maintenance operates.
unless you have concern for a particular long lived cell, it is best to destroy the tumour cell, and let the next cells in line replace them.
it is still a multifacet strategy being developed, inhibit the genetic properties of the tumour, and target the immunotype for destruction.
#TIL multiple myeloma went from being a death sentence in the 90's to quite manageable using a really old compound called thalidomide[1]. Though it sad that it was exploited for almost two decades to line the pockets of a dozen rich a*holes.
All in all what a century to be alive in, 100 years ago many people were living in mud huts globally (even in rural Europe) and now we have CRISPR, self-driving and hopefully UBI in a few years/decades. So much to look forward to.
Not exactly what you're looking for, but OWID has a bunch of great visualizations about cancer, including ones that really show the progress we've made (and how much we've yet to make!)
I think it's difficult to objectively quantify "effectively solved". A good source with loads of information about many diseases and their clinical status is OpenTargets, e.g. https://platform.opentargets.org/disease/EFO_0003860
Basically everything that was invented up to 3 years ago was invented without the help of "AI". And that includes "AI" itself, for we, humans, invented that too.
The foundational problem with cancer is that multicellular organisms rely on tight control of the cell division cycle and there are hundreds of ways that can go off kilter. The record of understanding and treatment is impressive, certainly, but the correct mental model is more ‘think of all the problems that can go wrong with a rocket launch - from contaminated fuel to software glitches’ than ‘here’s a list of cancers of different cell and organ types’.
Just as attacking such problems with rocket launches involves hundreds of different approaches, that’s the situation for cancer. I’d also point out that this is why it was really not trivial to identify microbial and viral causes of disease in the 19th century - especially since we now know that certain kinds of infectious disease can themselves result in cancer initiation. It’s definitely a hard set of problems.
I would also add, there was a concerted effort by industry to promote ‘inherent genetic malfunction’ as the cause of cancer in the late 1990s and early 2000s, but the reality is that exposure to industrial carcinogens tracks closely with a wide variety of cancers (skin, digestive tract, etc.). This was a very deceptive and dishonest approach to avoiding regulation.
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 tumor will evolve resistance. My guess is that cells will find ways to reject the lipid nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide sequence(s), either via modifications to the cell surface (preventing LNP uptake) or via changes to endosomal/lysosomal pathways (causing the mRNA payload to get degraded before it has a chance to be translated into protein).
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.
But cancer isn't an organism. Cancer cells in any specific individual may evolve that way, but "human cancers" as a group will not. (The only way they could is by evolving human DNA, but "survival of the fittest" pushes the opposite direction for that.)
Indeed, there's no "be a better/stronger cancer and spread more effectively to more hosts" the way there is with bacteria or a virus. It's not like the flu where we need a new shot every winter because every winter is a new flu.
Once we solve the cancers we know about, they're solved forever, with the one caveat that more people will live longer, so that will increase the window for eventually still ending up dying to one of the cancers that happens to have a non-evolved built in resistance to this or that treatment. Which is a great deal of course, especially if it's a treatment that sounds way less destructive of QoL than chemo, radiation, etc.
It's not very relevant here, but curiously some cancers are, in fact, contagious organisms. The most famous example is the devil facial tumour disease. Luckily cases of transmissible cancer in humans are extremely rare (if you count only transmission of cancer itself and not the cancerogenic agents).
Another curious case of "cancer being an organism" is the HeLa line derived from cervical cancer cells taken from a woman called Henrietta Lacks.
Nonetheless, we see the exact same resistance mechanisms to the same therapies recur across individuals, e.g. [0]. Convergent evolution is a harsh mistress.
There are some ideas about making it triggerable. So first you load the cells with a protein that is ready to start shredding but is inactive. Then you trigger it with a second compound.
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.
This will also cause problems because too many cells die at once. See the comments in other threads; killing the entire cancer at once is very hard on the body.
In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding would be infinitesimal.
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 effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
>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. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.
>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.
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 future. It just didn’t get the same news cycle, for whatever reason.
You're correct about CRISPR Cas9. The off-target affects are difficult to manage.
The paper describes Cas12a2. This is a different mechanism with discovery origins in - of all things - agriculture. It does not attempt in any way to reprogram cells. It uses a guide protein to locate a specific mutation with exacting precision and, when it activates, unleashes total destruction of the cell.
The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
Source: I have personally funded novel research based on Cas12a2 for an undruggable condition I have. I have personally seen my condition "cured" in vitro using this technology and it left all of my WT cells unharmed. Some of the researchers I've funded are co-authors in the paper linked. I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
Have you written about your experience anywhere? It would be interesting to see how you approached the research sector as a layperson. Are there any plans to move to in vivo? Best of luck with your research!
We did whole genome crispr designs at my last university job. Can confirm that off target effects are an issue with cas9. Pattern matching across the genome to see if a design is unique takes some time. These were interesting pipelines to work on.
It’s only a matter of time before the next better thing shows up.
I know nothing about this field, but I imagine the actual problem is how do you deliver the Cas12a2 protein to each individual cancer cell compare to a viral gene therapy?
If it were to work, gene therapy as-is would be possible. Which it is not,
not even for those overpriced therapies. I have no doubt that sooner or later
it will happen, as the problem space is finite, not infinite, but I simply
don't see the correlation here.
> The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
So what does this change exactly? Humans defined it as "undruggable conditions". You can reason this is an improvement, but I still see it in failure-territory. If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.
> I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
How does "answering questions" offset the technology being inferior right now?
Devils advocate, I also vehemently shat on RNAi therapeutics a decade back. We do have RNAi therapies in market now though. I do think Crispr will find its place similarly.
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.
CRIPSR was a game-changer for genetics research. A lot of gene knockout studies use CRISPR. However, it was always weirdly overhyped for clinical use from the beginning and this was obvious to anyone with a genetics background.
The public in general doesn't have a good understanding of basic genetics and I blame high school science curriculums for not covering it well enough. Too much time is wasted on Mendelian genetics without covering the Central Dogma.
You basically cannot "edit" your somatic DNA in a meaningful wholesale way since every single cell in your body has a copy of the DNA, and it's a foolish endeavor. What you can conceivably edit to good effect is your germline DNA, stem cell DNA, or modify mRNA expression (e.g. retinoids; yes putting retinol/adapalene cream on your face is "gene therapy"), or introduce foreign mRNA for your translation machinery to co-opt (e.g. mRNA vaccines).
I disagree that it's "gene therapy" to affect the natural regulation of mRNA production. If that were true then the term "gene therapy" loses its meaning, as just about everything changes the expression of mRNA. You can probably do so somewhere just by thinking really hard about it.
Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.
It was a game changer in terms of making things cheaper and a little easier. However the actual functionality was still possible with other methods. Zinc finger nucleases for example. Knockdown via RNAi is often still done because a knockout target may be inviable, and it is pretty cheap and easy to knockdown in most model systems.
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.
it's revolutionary in genetic research, allows us to observe cells with specific gene knockouts, over activations, etc. it's just very hard to deliver to a whole system
CRISPR is foremost a research tool. Calling it "extremely overhyped" without restricting it medical treatment seems disingenuous.
The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't find it surprising that merely 14 years later, there's only one approved treatment. From discovery to approval, drug development often takes 10-15 years, and often much longer for novel techniques. So I'd say it too early to call it overhyped for treatments.
Finally, I think we'll see a lot of treatments that don't use CRISPR-Cas9, but related gene editing techniques, but it'll take another 10 to 20 years.
Take a look at https://en.wikipedia.org/wiki/MRNA_vaccine#History for how long another novel technique has been in development before it became really widespread with the mrna-based covid-19 vaccines.
Background on this question: CRISPR-Cas is a naturally occurring process in bacteria that is used to adapt to viral attacks. We've coopted the system for use in mammals.
As far as I know a few labs in this space are operating under the basic question, "why haven't viruses killed everything by now?"
So this category of research is more or less the answer.
> Do mammals have a CRISPR analog?
Not exactly. There are things like https://en.wikipedia.org/wiki/Ribonuclease_L that nuke cells and are stimulated by interferons. This might be why interferon injections are common chronic therapeutics for diseases in this space.
The closest thing we have is probably whatever adaptability B or T cells can muster on their own? I'm sure someone lurking in the comments has a better answer.
I hope this finally works out. I remember almost exactly ten years ago I got excited about one of these proposed cancer cures, tried to talk about it at lunch with my coworkers, and they laughed at me for believing.
I'm pretty optimistic. I think it's a threshold question where we need a number of basic technologies to all get over certain bars before the floodgates start to open.
Over the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're starting to see it finally as so many different technologies have gotten so cheap, fast, and good.
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?
The floodgates open = the market will see that at least some of that can actually work and make money => they will pour funding => new approaches built on that funding will start working, too?
Real in vivo genetic engineering isn't going away and will indeed be a powerful tool to face cancer. Any particular effort is doubtful because this is a journey measured in decades. It is not the same story as any one particular wonder drug fizzling out to nothing, it is a class of tools that is maturing into the realm of early therapeutic deployment.
Cancer treatments are really scary things. There are all sorts of impacts that we have no idea about when using drugs that fundamentally attack pieces of our own body.
My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing
drugs. Some of the side effects included:
* Her heart stopping during a drug infusion. This happened multiple times over the 18 months of treatment.
* Disseminated fungal infections.
* Sepis because holes were developing in her GI tract.
This is just a sampler of the horrible effects.
This was a good response. Other patients just died from the drug combination.
This is what going slowly looks like in the world of cancer treatment.
We relax ‘do no harm’ quite a bit when the alternative is certain death. People like to try stuff in order to hang on to hope. Towards the end I became convinced that she made the wrong choice to do aggressive interventions. Quality of life was very bad.
On the other hand, she gave it her all trying to survive. Hopefully that was satisfying for her.
The point of going slowly is that we make sure something works, even if it has these bad side affects. Do we try experimental drugs with worse effects so that we can find effective ones faster? There are brave souls out there who will participate in clinical trials or experimental exceptions
That's a good article with a good point. As a caregiver impatiently waiting for Daraxonrasib, I can at least acknowledge that the institutional machinery is going as fast as it can. I've litterally witnessed a trial patient in the first cohort of a drug (that went no further) be rushed from infusion to the hospital; the trial process cannot be sped up from its current state without endangering lives.
My father's been using it since April. It's a little cumbersome and only improves overall survival rates by about two months over chemo alone, but we're hoping that it helps him remain relatively healthy until Daraxonrasib becomes available.
> Much like other CRISPR therapies, delivery is a critical challenge, i.e., getting the large genome-cutting enzyme to all the targeted cells efficiently.
makes me think this is in vitro so far. So, years to decades away from being available for actual treatment in humans. Still good news.
Basically the issue is often that gene therapies end up in the liver since its the livers job to detoxify, but that may cause a dangerous immune response if the immune system notices it in the liver and attacks the organ, since the person could die from the damage.
I’m assuming this has been tried, but why doesn’t nano-encapsulated mRNA (that then makes the CRISPR sequences in cells) or whatever the peptide injectors do solve the problem?
You can target an individual by injecting that very individual with something lethal.
If that's not what you want, you'd need something like a virus to spread it. But then you have to ask yourself: what if that virus mutates? The specialization to certain gene markers is an evolutionary disadvantage, so evolution will tend to make it lose that restriction. Ooops.
Old concern, but it really doesn't work that way. Genetics don't respect human ideas like "nationalities" or "borders" - the targeting you can get by selecting on singular DNA variants is coarse enough to make ICBMs look like precision weapons.
Like many things of this nature, people keep bringing it up because it sounds Very Scary and Very Dystopian - not because it's worth giving an actual fuck about.
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.
In order to kill all cancer cells in the body, it probably needs to be delivered to every single cell in the organism, and scan the nucleus of that cell. Viruses usually don't infect every single cell, just a small percentage.
So one needs to figure out a delivery method that is efficient enough, and that doesn't elicit an immune response. But I guess one can analyze the cancer in the lab and figure out which receptors it expresses, and then bind to those? We could have a toolkit of different delivery methods, tailored for each patient's cancer.
What economic / political model would cause the society to prioritize this over adtech? It seems so unsettling that brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
> 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.) More precisely counted, it probably doesn’t exceed $10bn.
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 approval reform. An ambitious example would be allowing conditional Market approval after Phase 2 and treating phase 3 deliverables as post-market commitments.
Advancing the revenue curve two to three years while maintaining the same patent expiration dates can dramatically change the ROI of a pharmaceutical development program.
Beyond this, even conditional Market allowance allows firms to better gauge Market interest and validate Financial investment models sooner.
Similarly, there's also some really low hanging fruit in this area to help manufacturers get to Market faster. For example, the FDA approval of trade names and label content is one of the last steps in Market authorization. Moving this earlier in the process would help products itself sooner and start producing Revenue sooner. Imagine having your billion dollar annual revenue shift out a quarter because the FDA wanted some last minute change to how a cartoon belly button looks in the instructions for use.
The bargaining dynamics are stacked against biology researchers at every stage of their career, from needing years and years of unrelated performance to be admitted to terribly expensive programs before they can begin to do experiments, to requiring costly equipment and resources to work, to needing to work with a small number of very powerful companies.
As a result, life science researchers are more price-taking than proce-setting when it comes to their wages / salary. If money is the motivator, then the market as-is isn’t addressing this one.
And when you can measure how effective those ads are in changing human behavior; it's easier for businesses to spend there. As an American, I would love it if pharmaceutical companies couldn't market to consumers. It would free up money for research or lower prices.
I said it elsewhere but I'll say it here - we need one of the top 10 richest people in the world - the Bezos, the Musks etc - to suddenly get very interested at a personal level about cancer treatment.
Bezos and several other billionaires stuck a load of money into Altos Labs, an organization that studies aging and longevity.
Cancer prevention is downstream from that, as cancer frequency grows exponentially with age. If you can truly rejuvenate a person, you will also reduce their risk of cancer.
I don't think an economic model would work. Only a political one would work where the government would redirect a lot of funds towards this, making it a lucrative profession.
Adtech works because there is a lot of money in it. There is a lot of money in it because people seek quick entertainment, and we have a LOT of people driving the demand.
Now compare that to cancer research. There's no short term gratification about it.
>brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
And even more brilliant minds are defeating it, every day. I have doubts about how useful they would be in a research lab.
There's a fair bit of frequency illusion involved here. A lot of brilliant human minds aren't, in fact, working on ad tech, and a lot of the people working on ad tech aren't, in fact, that brilliant (as evidenced by them working adversarially against their own fellow humans, for one).
There's a wide world outside big tech, Silicon Valley, and software in general. It only tends to be a bit less visible online.
Not sure why you're getting downvoted, it's quite an interesting (and important!) question.
Also wonder, outside of politics and economics, whether there's a social and cultural component that can contribute. TV shows, movies, books, and other forms of media that put science and scientists in the spotlight in a positive light can be tremendously inspirational.
So how do drugs like this get fast tracked so that people who are in danger of dying can exercise their freedom and opt into experimental treatments very easily
First thing to remember: cancer drugs attack human cells. Because of this they can very unexpected and traumatic side-effects.
Because of this initial trials consume lots of medical staff to deal with the potential side effects. Normal side effects for cancer treatments include:
* Your gut lining dissolves, your shit leaks into your body cavity, and you get sepsis.
* Your heart stops during the infusion.
* Cumulative poisoning that nobody understands. (E.g. some agents have lifetime limits, and if you go beyond that, then you die. Guess how we found out.)
* Your immune system, and you get things like disseminated fungal infections.
The danger of side-effects like this requires a medical team largely dedicated to the experimental patients.
This puts a limit on how many patients you can put into a trial. I'm under the impression that cancer trials are pretty much always full.
Same problem with chemo and radiation. A tumor may start off with a single cancerous mutation, but by the time it spreads there may be several. Once the cell repair machinery has been broken, the cancer cells are prone for more mutations.
Chemo, radiation, and CRISPR will kill everything it can reach that is susceptible. That leaves everything that was unreachable or resistant behind to start growing again.
Kill cancer cells is easy. Killing ONLY cancer cells is very hard.
This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.
> This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.
CRISPR was the cause of a huge patent case and likely led to a change in US patent law because of the impracticability of deciding who did something first in the laboratory.
It continues to influence research as some nations took a while to decide how they would resolve their own researchers' CRISPR claims with respect to MIT/UC Berkeley.
And yet... all the research has continued apace.
Edit: the CRISPR patent cases are continuing even today
Over on reddit people were debating whether cancer should be cured since it disproportionately affects rich people and it made me realise how far reddit has fallen. It's just a botnet now to manipulate elections.
I'm certain that is not a mainsteam opinion on reddit, but by its nature you will be able to find arbitrarily stupid opinions in individual echo chambers
After we launched our startup, we had all sorts of folks reach out to sell their GTM services. I went with one group from Vietnam that would make engagement bait Reddit questions with some accounts, and advertise our product in the comments section with others. It was expensive but it worked
Do you think (or care) about the ethics of this sort of behavior? Do you consider it unethical and if you do, under what conditions would you decide to do it anyway?
Reddit is a huge danger to society. There's no doubt that subs about specific non political (and non popular) topics are hugely beneficial, the overall damage the echo chambers do still outweigh these benefits.
The flip side is that "fuck cancer" is a shibboleth there, to the point where a headline, "[Bad person] has contracted cancer" has every comment thread starting with "First, fuck cancer."
I would imagine the charitable characterization of that discussion is much closer to “awesome, this will mean the Peter Thiels and Elon Musks of the world will live to 150 while both me and my children will be dead long before this trickles down to regular people” vs. “we shouldn’t cure cancer”.
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 biological problem and achieving the next milestone in solving it. We might have "AI", but we also have brilliant minds right now that are speeding up development to a pace that would be unimaginable just few years ago.
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.
I wouldn't understate advances in Melanoma treatment. Immunotherapies have absolutely changed the game in that space. It's not a curable cancer (few are) but it's far more treatable.
1 reply →
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.
That's understating the progress by a lot - many cancers are a lot more survivable now than previously with better chemo/radio/surgery + immunotherapies + car-t etc etc
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.
9 replies →
There are lots of other success stories too. For example there is a reason why Keytruda is the most valuable medicine globally -- it does amazing things against melanoma and lung cancer
They are starting to ship this out across the country. My uncle has pancreatic cancer and is hoping to get a shipment in the next two months. Apparently you discontinue chemo while on it because it’s so unnecessary at that point.
I think some class of melanomas and small-cell lung cancers went from 6 month survival to now completely "cureable" using immunology drugs
1 reply →
It's difficult to do that because we don't even really know how many cancers there are.
Cancer is best understood as a family of tens of thousands of diseases. They're a whole range of different genetic changes that can happen which result in similar categories of symptoms and consequences. They can also be incredibly complex, such as being the result of hundreds of stacking genetic defects acquired over a lifetime. There can be a thousand varieties of one specific type of lung cancer, and they might all react differently. Some of our solutions might work on a lot of them, but others might only work on a handful. And we're at the beginning of figuring all this out.
CRISPR may eventually allow us to genetically profile a cancer and design highly targeted medications to cure them, but we don't know yet how well it will work. It may only work on a portion of them. It may have worse outcomes than chemotherapy or radiation. It's nice to think that we're going to find a magic solution to the entire problem, but things almost never work that way. I think we're going to be able to resolve a wide range of issues, but I don't think it will really cure cancer as a whole.
> Cancer is best understood as a family of tens of thousands of diseases
There's a site that lists the AWS instance types, so maybe...
you should probably look at oncogenes in general.
https://en.wikipedia.org/wiki/Oncogene
at the simplest level, the particular gene, and particular perturberance, sets the "type" of cancer.
there will most often be additional genetic abnormalities giving nuance to the character of the oncotype.
the tumour is originated from a cell type of specific differentiation, and developmental potency, further widening the pool of possible cancer type.
immunotype of cancer also sets the relationship between cancer and the body.
the cells of the body are setup for a functional death and replacement so when you try to rescue a particular cell [or cohort] you are fighting against how the grand scheme of tissue maintenance operates.
unless you have concern for a particular long lived cell, it is best to destroy the tumour cell, and let the next cells in line replace them.
it is still a multifacet strategy being developed, inhibit the genetic properties of the tumour, and target the immunotype for destruction.
https://en.wikipedia.org/wiki/Cancer_immunology
#TIL multiple myeloma went from being a death sentence in the 90's to quite manageable using a really old compound called thalidomide[1]. Though it sad that it was exploited for almost two decades to line the pockets of a dozen rich a*holes.
[1](https://www.propublica.org/podcast/revlimid-cancer-drugs-fda...)
All in all what a century to be alive in, 100 years ago many people were living in mud huts globally (even in rural Europe) and now we have CRISPR, self-driving and hopefully UBI in a few years/decades. So much to look forward to.
Not exactly what you're looking for, but OWID has a bunch of great visualizations about cancer, including ones that really show the progress we've made (and how much we've yet to make!)
https://ourworldindata.org/cancer
Exactly.Now these are the kind of matters the world should be more inclined to invest in.
I think it's difficult to objectively quantify "effectively solved". A good source with loads of information about many diseases and their clinical status is OpenTargets, e.g. https://platform.opentargets.org/disease/EFO_0003860
Let the record reflect that I had this exact idea 2 years ago but never finished it, and remembered it this morning.
> We might have "AI" ...
Basically everything that was invented up to 3 years ago was invented without the help of "AI". And that includes "AI" itself, for we, humans, invented that too.
So yup, humans can be quite resourceful.
The foundational problem with cancer is that multicellular organisms rely on tight control of the cell division cycle and there are hundreds of ways that can go off kilter. The record of understanding and treatment is impressive, certainly, but the correct mental model is more ‘think of all the problems that can go wrong with a rocket launch - from contaminated fuel to software glitches’ than ‘here’s a list of cancers of different cell and organ types’.
Just as attacking such problems with rocket launches involves hundreds of different approaches, that’s the situation for cancer. I’d also point out that this is why it was really not trivial to identify microbial and viral causes of disease in the 19th century - especially since we now know that certain kinds of infectious disease can themselves result in cancer initiation. It’s definitely a hard set of problems.
I would also add, there was a concerted effort by industry to promote ‘inherent genetic malfunction’ as the cause of cancer in the late 1990s and early 2000s, but the reality is that exposure to industrial carcinogens tracks closely with a wide variety of cancers (skin, digestive tract, etc.). This was a very deceptive and dishonest approach to avoiding regulation.
Have you asked Claude to pull this and graph it over time? It could build a static site as well.
Isn’t this likely to lead to inaccurate data? I wouldn’t know enough about the domain to fact-check Claude.
Have you tried just mashing on the keyboard and seeing if a great comment comes out?
Here's their preprint from a month ago, in case you can't access the Nature paper: https://www.biorxiv.org/content/10.64898/2026.05.08.723607v1
Nature - https://www.nature.com/articles/s41586-026-10738-7
[dead]
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 tumor will evolve resistance. My guess is that cells will find ways to reject the lipid nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide sequence(s), either via modifications to the cell surface (preventing LNP uptake) or via changes to endosomal/lysosomal pathways (causing the mRNA payload to get degraded before it has a chance to be translated into protein).
[0] https://pubmed.ncbi.nlm.nih.gov/28575452/
[1] https://www.nature.com/articles/s41598-018-30205-2
[2] https://www.nature.com/articles/s41467-020-18875-x
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.
But cancer isn't an organism. Cancer cells in any specific individual may evolve that way, but "human cancers" as a group will not. (The only way they could is by evolving human DNA, but "survival of the fittest" pushes the opposite direction for that.)
Indeed, there's no "be a better/stronger cancer and spread more effectively to more hosts" the way there is with bacteria or a virus. It's not like the flu where we need a new shot every winter because every winter is a new flu.
Once we solve the cancers we know about, they're solved forever, with the one caveat that more people will live longer, so that will increase the window for eventually still ending up dying to one of the cancers that happens to have a non-evolved built in resistance to this or that treatment. Which is a great deal of course, especially if it's a treatment that sounds way less destructive of QoL than chemo, radiation, etc.
5 replies →
It's not very relevant here, but curiously some cancers are, in fact, contagious organisms. The most famous example is the devil facial tumour disease. Luckily cases of transmissible cancer in humans are extremely rare (if you count only transmission of cancer itself and not the cancerogenic agents).
Another curious case of "cancer being an organism" is the HeLa line derived from cervical cancer cells taken from a woman called Henrietta Lacks.
Nonetheless, we see the exact same resistance mechanisms to the same therapies recur across individuals, e.g. [0]. Convergent evolution is a harsh mistress.
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/
There are some ideas about making it triggerable. So first you load the cells with a protein that is ready to start shredding but is inactive. Then you trigger it with a second compound.
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.
2 replies →
This will also cause problems because too many cells die at once. See the comments in other threads; killing the entire cancer at once is very hard on the body.
1 reply →
Surely a far simpler way to evolve resistance would be a trivial mutation in the p53 transcript that the guide RNA is looking for.
In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding would be infinitesimal.
1 reply →
[dead]
[dead]
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 effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
I'm no expert, but p53 is known as "the guardian of the genome."
If p53 is reactivated, the cancer cell dies.
https://en.wikipedia.org/wiki/P53
Perhaps a different mutation that disables p53 could evade the pattern match.
This article is all about p53.
Edit: This section of the wiki best explains this critical cellular component...
p53 regulates cell cycle progression, apoptosis, and genomic stability through multiple mechanisms:
-Activates DNA repair proteins in response to DNA damage, suggesting a potential role in aging.
-Arrests the cell cycle at the G1/S checkpoint upon DNA damage, allowing time for repair before progression.
-Initiates apoptosis if the damage is beyond repair.
-Essential for the senescence response triggered by short telomeres.
>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. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.
2 replies →
>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.
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 future. It just didn’t get the same news cycle, for whatever reason.
You're correct about CRISPR Cas9. The off-target affects are difficult to manage.
The paper describes Cas12a2. This is a different mechanism with discovery origins in - of all things - agriculture. It does not attempt in any way to reprogram cells. It uses a guide protein to locate a specific mutation with exacting precision and, when it activates, unleashes total destruction of the cell.
The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
Source: I have personally funded novel research based on Cas12a2 for an undruggable condition I have. I have personally seen my condition "cured" in vitro using this technology and it left all of my WT cells unharmed. Some of the researchers I've funded are co-authors in the paper linked. I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
Have you written about your experience anywhere? It would be interesting to see how you approached the research sector as a layperson. Are there any plans to move to in vivo? Best of luck with your research!
18 replies →
We did whole genome crispr designs at my last university job. Can confirm that off target effects are an issue with cas9. Pattern matching across the genome to see if a design is unique takes some time. These were interesting pipelines to work on.
It’s only a matter of time before the next better thing shows up.
I know nothing about this field, but I imagine the actual problem is how do you deliver the Cas12a2 protein to each individual cancer cell compare to a viral gene therapy?
7 replies →
So how does Cas12a2 mitigate off-target effects?
If it were to work, gene therapy as-is would be possible. Which it is not, not even for those overpriced therapies. I have no doubt that sooner or later it will happen, as the problem space is finite, not infinite, but I simply don't see the correlation here.
> The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
So what does this change exactly? Humans defined it as "undruggable conditions". You can reason this is an improvement, but I still see it in failure-territory. If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.
> I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
How does "answering questions" offset the technology being inferior right now?
1 reply →
This is wild, have you written about it publicly, or can you expand on it here?
1 reply →
May I ask, how much money you have spent so far on this effort?
Devils advocate, I also vehemently shat on RNAi therapeutics a decade back. We do have RNAi therapies in market now though. I do think Crispr will find its place similarly.
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.
CRIPSR was a game-changer for genetics research. A lot of gene knockout studies use CRISPR. However, it was always weirdly overhyped for clinical use from the beginning and this was obvious to anyone with a genetics background.
The public in general doesn't have a good understanding of basic genetics and I blame high school science curriculums for not covering it well enough. Too much time is wasted on Mendelian genetics without covering the Central Dogma.
You basically cannot "edit" your somatic DNA in a meaningful wholesale way since every single cell in your body has a copy of the DNA, and it's a foolish endeavor. What you can conceivably edit to good effect is your germline DNA, stem cell DNA, or modify mRNA expression (e.g. retinoids; yes putting retinol/adapalene cream on your face is "gene therapy"), or introduce foreign mRNA for your translation machinery to co-opt (e.g. mRNA vaccines).
Edit every cell? No. Edit enough cells to impact health outcomes for a meaningful period of time? [Yes](https://www.youtube.com/watch?v=J3FcbFqSoQY)
1 reply →
I disagree that it's "gene therapy" to affect the natural regulation of mRNA production. If that were true then the term "gene therapy" loses its meaning, as just about everything changes the expression of mRNA. You can probably do so somewhere just by thinking really hard about it.
Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.
It was a game changer in terms of making things cheaper and a little easier. However the actual functionality was still possible with other methods. Zinc finger nucleases for example. Knockdown via RNAi is often still done because a knockout target may be inviable, and it is pretty cheap and easy to knockdown in most model systems.
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.
it's revolutionary in genetic research, allows us to observe cells with specific gene knockouts, over activations, etc. it's just very hard to deliver to a whole system
Viral vector delivery is indeed harder to sell with PopSci, what with movies like "I am Legend".
Great first half of a movie, by the way. Up there with Sunshine for "Sit down for a great hour-long ambiance".
I usually end Legend after the mannequin trap, and end Sunshine after the transit of mercury.
You're confusing the beurocratic FDA stamp of approval with safety and effectiveness. Those are not the same thing.
Bingo! CRISPR has an advantage of being relatively easy to describe to a layman, giving it a PR advantage.
So is the "idea" of microchips in vaccines. Should we just give up and let everything else have the PR advantage
CRISPR is foremost a research tool. Calling it "extremely overhyped" without restricting it medical treatment seems disingenuous.
The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't find it surprising that merely 14 years later, there's only one approved treatment. From discovery to approval, drug development often takes 10-15 years, and often much longer for novel techniques. So I'd say it too early to call it overhyped for treatments.
Finally, I think we'll see a lot of treatments that don't use CRISPR-Cas9, but related gene editing techniques, but it'll take another 10 to 20 years.
Take a look at https://en.wikipedia.org/wiki/MRNA_vaccine#History for how long another novel technique has been in development before it became really widespread with the mrna-based covid-19 vaccines.
Why does it take 20 years? Except, of course, that it does not work nowhere near as well as it is being promoted - aka hyped.
mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
2 replies →
Do mammals have a CRISPR analog?
Background on this question: CRISPR-Cas is a naturally occurring process in bacteria that is used to adapt to viral attacks. We've coopted the system for use in mammals.
As far as I know a few labs in this space are operating under the basic question, "why haven't viruses killed everything by now?"
So this category of research is more or less the answer.
> Do mammals have a CRISPR analog?
Not exactly. There are things like https://en.wikipedia.org/wiki/Ribonuclease_L that nuke cells and are stimulated by interferons. This might be why interferon injections are common chronic therapeutics for diseases in this space.
The closest thing we have is probably whatever adaptability B or T cells can muster on their own? I'm sure someone lurking in the comments has a better answer.
“Virus” - that’s why.
[dead]
[dead]
Yes! I have a genetic disease that will take me out in my 70s and I’m really hoping CRISPR gets to it before I do!
I don't mean to sound insensitive, but don't most people die around age 70-80?
Life expectancy in many countries is mid 80s.
3 replies →
A lot of people's genes will take them out in their 70s but cheers to crispy
Very true!
I hope for you and others that they will!
I hope this finally works out. I remember almost exactly ten years ago I got excited about one of these proposed cancer cures, tried to talk about it at lunch with my coworkers, and they laughed at me for believing.
I'm pretty optimistic. I think it's a threshold question where we need a number of basic technologies to all get over certain bars before the floodgates start to open.
Over the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're starting to see it finally as so many different technologies have gotten so cheap, fast, and good.
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?
13 replies →
the public experiences biotechnology as decades of nothing, followed by years of everything once bottlenecks align
1 reply →
The floodgates open = the market will see that at least some of that can actually work and make money => they will pour funding => new approaches built on that funding will start working, too?
Real in vivo genetic engineering isn't going away and will indeed be a powerful tool to face cancer. Any particular effort is doubtful because this is a journey measured in decades. It is not the same story as any one particular wonder drug fizzling out to nothing, it is a class of tools that is maturing into the realm of early therapeutic deployment.
For the state of new cancer-killing drugs and bottlenecks getting them approved, see also the top few posts on https://www.writingruxandrabio.com/archive
The post on AI and and cures for cancer is https://www.writingruxandrabio.com/p/a-response-to-dario-amo... .
Cancer treatments are really scary things. There are all sorts of impacts that we have no idea about when using drugs that fundamentally attack pieces of our own body.
My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included:
This is just a sampler of the horrible effects.
This was a good response. Other patients just died from the drug combination.
This is what going slowly looks like in the world of cancer treatment.
Sorry you both experienced that. We did too.
We relax ‘do no harm’ quite a bit when the alternative is certain death. People like to try stuff in order to hang on to hope. Towards the end I became convinced that she made the wrong choice to do aggressive interventions. Quality of life was very bad.
On the other hand, she gave it her all trying to survive. Hopefully that was satisfying for her.
The point of going slowly is that we make sure something works, even if it has these bad side affects. Do we try experimental drugs with worse effects so that we can find effective ones faster? There are brave souls out there who will participate in clinical trials or experimental exceptions
5 replies →
That's a good article with a good point. As a caregiver impatiently waiting for Daraxonrasib, I can at least acknowledge that the institutional machinery is going as fast as it can. I've litterally witnessed a trial patient in the first cohort of a drug (that went no further) be rushed from infusion to the hospital; the trial process cannot be sped up from its current state without endangering lives.
> As a caregiver impatiently waiting for Daraxonrasib
Same here. Are you and your care recipient familiar with the Optune Pax device that the FDA approved in February?
https://www.fda.gov/news-events/press-announcements/fda-appr...
My father's been using it since April. It's a little cumbersome and only improves overall survival rates by about two months over chemo alone, but we're hoping that it helps him remain relatively healthy until Daraxonrasib becomes available.
1 reply →
The article is pretty light on details, but
> Much like other CRISPR therapies, delivery is a critical challenge, i.e., getting the large genome-cutting enzyme to all the targeted cells efficiently.
makes me think this is in vitro so far. So, years to decades away from being available for actual treatment in humans. Still good news.
Basically the issue is often that gene therapies end up in the liver since its the livers job to detoxify, but that may cause a dangerous immune response if the immune system notices it in the liver and attacks the organ, since the person could die from the damage.
I’m assuming this has been tried, but why doesn’t nano-encapsulated mRNA (that then makes the CRISPR sequences in cells) or whatever the peptide injectors do solve the problem?
Yeah. With cancer, delivering to 99% of the cells won't cut it, the surviving 1% will quickly grow back.
(removed)
You can target an individual by injecting that very individual with something lethal.
If that's not what you want, you'd need something like a virus to spread it. But then you have to ask yourself: what if that virus mutates? The specialization to certain gene markers is an evolutionary disadvantage, so evolution will tend to make it lose that restriction. Ooops.
1 reply →
Old concern, but it really doesn't work that way. Genetics don't respect human ideas like "nationalities" or "borders" - the targeting you can get by selecting on singular DNA variants is coarse enough to make ICBMs look like precision weapons.
Like many things of this nature, people keep bringing it up because it sounds Very Scary and Very Dystopian - not because it's worth giving an actual fuck about.
2 replies →
I suppose it could also be used to assassinate specific persons with the precision of DNA matching. Like FOXDIE.
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.
In order to kill all cancer cells in the body, it probably needs to be delivered to every single cell in the organism, and scan the nucleus of that cell. Viruses usually don't infect every single cell, just a small percentage.
So one needs to figure out a delivery method that is efficient enough, and that doesn't elicit an immune response. But I guess one can analyze the cancer in the lab and figure out which receptors it expresses, and then bind to those? We could have a toolkit of different delivery methods, tailored for each patient's cancer.
Gene splicing ATGC nucleotide.
[1]: https://www.clinicalcorrelations.org/2019/02/22/the-history-...
What economic / political model would cause the society to prioritize this over adtech? It seems so unsettling that brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
> 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.) More precisely counted, it probably doesn’t exceed $10bn.
[1] https://phrma.org/blog/phrma-member-companies-rd-investments...
[2] https://www.science.org/content/article/final-nih-budget-202...
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 approval reform. An ambitious example would be allowing conditional Market approval after Phase 2 and treating phase 3 deliverables as post-market commitments.
Advancing the revenue curve two to three years while maintaining the same patent expiration dates can dramatically change the ROI of a pharmaceutical development program.
Beyond this, even conditional Market allowance allows firms to better gauge Market interest and validate Financial investment models sooner.
Similarly, there's also some really low hanging fruit in this area to help manufacturers get to Market faster. For example, the FDA approval of trade names and label content is one of the last steps in Market authorization. Moving this earlier in the process would help products itself sooner and start producing Revenue sooner. Imagine having your billion dollar annual revenue shift out a quarter because the FDA wanted some last minute change to how a cartoon belly button looks in the instructions for use.
1 reply →
The bargaining dynamics are stacked against biology researchers at every stage of their career, from needing years and years of unrelated performance to be admitted to terribly expensive programs before they can begin to do experiments, to requiring costly equipment and resources to work, to needing to work with a small number of very powerful companies.
As a result, life science researchers are more price-taking than proce-setting when it comes to their wages / salary. If money is the motivator, then the market as-is isn’t addressing this one.
The US government funds a lot of these programs, as they are obviously in the public interest. Until one man decided to stop it.
When you reframe ads as "control of human attention" it suddenly makes a lot more sense why so many resources are poured into them.
And when you can measure how effective those ads are in changing human behavior; it's easier for businesses to spend there. As an American, I would love it if pharmaceutical companies couldn't market to consumers. It would free up money for research or lower prices.
I said it elsewhere but I'll say it here - we need one of the top 10 richest people in the world - the Bezos, the Musks etc - to suddenly get very interested at a personal level about cancer treatment.
Then the money will flow.
Zuck has a lot of money in biohub iirc
Bezos and several other billionaires stuck a load of money into Altos Labs, an organization that studies aging and longevity.
Cancer prevention is downstream from that, as cancer frequency grows exponentially with age. If you can truly rejuvenate a person, you will also reduce their risk of cancer.
I don't think an economic model would work. Only a political one would work where the government would redirect a lot of funds towards this, making it a lucrative profession.
Adtech works because there is a lot of money in it. There is a lot of money in it because people seek quick entertainment, and we have a LOT of people driving the demand.
Now compare that to cancer research. There's no short term gratification about it.
>brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
And even more brilliant minds are defeating it, every day. I have doubts about how useful they would be in a research lab.
There's a fair bit of frequency illusion involved here. A lot of brilliant human minds aren't, in fact, working on ad tech, and a lot of the people working on ad tech aren't, in fact, that brilliant (as evidenced by them working adversarially against their own fellow humans, for one).
There's a wide world outside big tech, Silicon Valley, and software in general. It only tends to be a bit less visible online.
Humans are a bunch of hairless monkeys that have evolved to scam each other rather than hunt and gather food from Nature.
Not sure why you're getting downvoted, it's quite an interesting (and important!) question.
Also wonder, outside of politics and economics, whether there's a social and cultural component that can contribute. TV shows, movies, books, and other forms of media that put science and scientists in the spotlight in a positive light can be tremendously inspirational.
I remember seeing a comic strip about this exact argument but I can’t find it any more
But the real question all of us ask is: What about hairloss?
Apparently this group was a bit late. Here is the first group with the same approach
https://www.nature.com/articles/s41586-026-10466-y
[dead]
So how do drugs like this get fast tracked so that people who are in danger of dying can exercise their freedom and opt into experimental treatments very easily
First thing to remember: cancer drugs attack human cells. Because of this they can very unexpected and traumatic side-effects.
Because of this initial trials consume lots of medical staff to deal with the potential side effects. Normal side effects for cancer treatments include:
The danger of side-effects like this requires a medical team largely dedicated to the experimental patients.
This puts a limit on how many patients you can put into a trial. I'm under the impression that cancer trials are pretty much always full.
been hearing about CRISPR since I was in middle school. is there actually any new development here?
Can anyone point to some resources about how cancers might adapt to CRISPR treatments?
Same problem with chemo and radiation. A tumor may start off with a single cancerous mutation, but by the time it spreads there may be several. Once the cell repair machinery has been broken, the cancer cells are prone for more mutations.
Chemo, radiation, and CRISPR will kill everything it can reach that is susceptible. That leaves everything that was unreachable or resistant behind to start growing again.
Kill cancer cells is easy. Killing ONLY cancer cells is very hard.
This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.
> This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.
CRISPR was the cause of a huge patent case and likely led to a change in US patent law because of the impracticability of deciding who did something first in the laboratory.
It continues to influence research as some nations took a while to decide how they would resolve their own researchers' CRISPR claims with respect to MIT/UC Berkeley.
And yet... all the research has continued apace.
Edit: the CRISPR patent cases are continuing even today
https://news.berkeley.edu/2025/05/12/federal-appeals-court-s...
https://www.broadinstitute.org/crispr/journalists-statement-...
Cool. How can I help
Go CRISPR! I just lost a good friend Bobby to cancer who was a sweet kind man. Die cancer.
Jennifer Doudna again. What an amazing scientist. Wow.
just finished reading The Code Breaker, interesting stuff on Doudna & CRISPR
[dead]
[flagged]
Over on reddit people were debating whether cancer should be cured since it disproportionately affects rich people and it made me realise how far reddit has fallen. It's just a botnet now to manipulate elections.
I'm certain that is not a mainsteam opinion on reddit, but by its nature you will be able to find arbitrarily stupid opinions in individual echo chambers
I am not so certain
Just spend 15 minutes in /b/ and everything else will feel better.
After we launched our startup, we had all sorts of folks reach out to sell their GTM services. I went with one group from Vietnam that would make engagement bait Reddit questions with some accounts, and advertise our product in the comments section with others. It was expensive but it worked
Do you think (or care) about the ethics of this sort of behavior? Do you consider it unethical and if you do, under what conditions would you decide to do it anyway?
Reddit is a huge danger to society. There's no doubt that subs about specific non political (and non popular) topics are hugely beneficial, the overall damage the echo chambers do still outweigh these benefits.
4 replies →
The flip side is that "fuck cancer" is a shibboleth there, to the point where a headline, "[Bad person] has contracted cancer" has every comment thread starting with "First, fuck cancer."
I would imagine the charitable characterization of that discussion is much closer to “awesome, this will mean the Peter Thiels and Elon Musks of the world will live to 150 while both me and my children will be dead long before this trickles down to regular people” vs. “we shouldn’t cure cancer”.
[flagged]