I was fortunate to participate in the trial for this drug for over a year. It is nothing short of a miracle drug (although there is still more that can be done). I was forced to withdraw after the drug lost its effectiveness and my disease progressed. That said, though, for over a year all of my tumors either disappeared, shrank, or remained stable. For a disease that was largely considered a near-immediate death sentence, this drug is an absolute game change. I am eternally grateful for the scientists and researchers at RevMed.
The bigger deal about this is that KRAS was considered an "undruggable" target.
Recent advancements have allowed us to design biologics to do things we previously thought impossible, which broadens the horizons for other treatments in the future.
The Johns Hopkins Children's' Center is looking at trialing it for rhabdomyosarcoma, a particularly deadly form of cancer that primary targets children. If successful, this would represent a HUGE leap forward in its treatment.
Horrible disease. We just buried my wife’s father because of stage 4 pancreatic cancer. A month ago, he was still living his life as usual. Then he developed abdominal pain, was diagnosed, and died three weeks later.
I think we should also invest more in better diagnostics and early cancer detection. That could save many lives too.
This cancer is a pain. My father was extremely lucky, and was diagnosed early. Next up was months of chemo that left him to be a shell of himself. Then he could be operated. They removed parts of his stomach, his spleen and duodenum. And his whole pancreas.
Complications after his surgery meant he had two more. He is now, three weeks after the first operation learning to walk again. It will be an additional week or two untill he can eat. (Without the complication he would have been walking and eating two weeks after the first operation). Oh and he is a diabetic now, since they removed his pancreas.
Just crossing my fingers that he will get out of the hospital without any more complications, and adapt to the new life.
My mother's cousin just died from pancreatic cancer on Monday. She was in a trial for this drug and failed. Trying to figure out how I feel about this or how my family would.
Personally, I have epilepsy and am increasingly aware that while some paradigm-shifting treatments are on the horizon, they are a decade or so away and likely won't come to market in time to fully help me (particularly reverse small but accumulating damage caused by seizures). And that's a weird feeling.
Failing a treatment that has held promise for so many others and been heralded as paradigm-shifting is such a weird place to be. There's comfort in knowing others won't suffer, but loneliness is knowing you or a loved one still is.
Please remember that science is under attack in the United States - new proposals would gut the nih even beyond the horror that is ongoing. As a scientist I am horrified and I truly hope that we don’t abandon the usas historically strong investment in the future.
1. Trump has been trying to cut Science budgers by larger percentages for a while now. Congress has not let them.
2. NIH funding notice of awards has slowed to a crawl since Trump did not get his wish to cut Science funding.
3. Putting scientific funding under political control, instructing them to ignore the reviews conducted by peer scientists.
4. Have practically made international collaborations on grants impossible. An expert in Canada or Europe that would be great? Pretty much, too bad.
5. Pushing policies that make grants cancelable at any moment without need to have a justified reason, including potentially for exercising free speech, disagreeing with Administration doctrine, etc, or because you're ugly. This and the funding uncertainty makes planning difficult...just like business, stability/predictability matters.
6. Pushing policies that prevent funds to help cover costs of dissemination, including conference costs.
Could you explain how much the US spends on its science budget compared to peers? It would help us really understand how much he's cutting it and harming our science base if we knew the numbers. For example if we're spending 50% less than EU or Canada.
> Kindly share more details (about your claim that science is under attack in the United States)
Is of public knowledge that the National Science Foundation and funds for thousands of scientific projects were gutted by DOGE in 2025.
Each one of the research lines cut needed typically 10 years to grow, so Trump and GOP had destroyed an incredible amount of years of research just on 2025, with consequences probably extending into 2035 or so. Without any visible benefit for Americans, that had still seen their debt sky-rocketing while their taxes are spent in pools and sinks.
Trump has also assured to engrave into the brains of the whole scientific community that US is now an hostile place for students and researchers. The whole planet had seen the main universities attacked by Trump (with Harvard resisting, and Columbia losing their pride), the foreign students targeted by ICE and the department of Education eviscerated
Also the thousands of workers in USAID and Health and Human Services fired for fun. Without mentioning the DOGE mess done at the national nuclear safety administration with 400 essential workers fired and then asked to return to the job ASAP, please, please.
It pleases their voters. All the MAGAs I know think scientists are scammers, funded by Bill Gates, brewing up "fake" viruses to reduce the population and insert nanobots to track their movements.
They are all about science and research. What they don’t want is for scientific discoveries to be publicly available, because then it is harder to leverage them for absurd profit margins.
It is more than plausible that spending money on AI is spending money on healthcare. I believe with little certainty that AI will help us find new ways to fight disease, improve our health and live longer lives.
Actually, I think it's powerful to acknowledge when my beliefs are weak. I still believe it - I think it's true, and I don't have any conflicting beliefs. But still it would not take a lot of evidence to change my mind, and since this is a prediction about the future, I will not be very surprised to find out I was wrong.
Another ongoing HN thread from yesterday around some exciting cancer treatment breakthroughs, this time with a CRISPR Cas12a2 mechanism: https://news.ycombinator.com/item?id=48505231
This subthread there is a fascinating explainer about one user's journey into funding and incentivizing research into their own rare form of blood cancer, and how they are able to push forward the state of the art: https://news.ycombinator.com/item?id=48506997 - something of a modern-day (and more accurate) Lorenzo's Oil!
I’m surprised Michael Levin’s research hasn’t expanded much beyond a certain YouTube media bubble. They’re able to start and stop cancer growth with only voltage changes between cells, likewise they can also trigger regeneration or anatomical changes using voltage changes. His research seems to suggest a lot of important anatomical plans are stored in an electric field around the body, not in the DNA. This model’s explanation for cancer is that some cells become disconnected from this field and start growing independently of the overall body plan.
I love his work (even though I know little more than what he says in interviews). I am also surprised it's not more widely known / applied. I am very skeptical of conspiracy-minded thinking, so I'd much rather assume his and his team's work hasn't reached escape velocity from obscurity. Especially with larger industries, it takes time and significant breakthroughs to become "a household name", so to speak.
They are working on getting in vivo studies going from what I remember - it's going to take a positive result in a trial on real patients to get attention - that's just how medicine works. You have to show it actually improves longevity and/or patient quality of life before anyone has a reason to care.
Do you think we don't have cure already for cancers???
Look for how much money the pharmaceutic cartels make annually, that is why these "drugs" aka cure will never ever be released because its side effects are still unknown.
i remember so much excitement around radioligand therapies like 177Lu-PSMA-617 being better than chemo and with way way less sides . And great improvements in pfs and os.
didnt seem to have lived up to the promise. seemed to have accelerated prostate cancer for my father who passed away in mere three months after first dose.
As is often the case, the title is hyperbolic. The discovery applies to 20% of tumors, and "one of cancer's significant defenses" or "a key weakness of cancer" would be more accurate.
That said, I'll happily take "we discovered a key weakness in 20% of cancers," please and thank you.
I'm no expert, and don't know if it applies in this case, but for a cancer I had (lymphoma) I was told that aggressive can often be easier to treat or "cure" (as defined by survival rates, etc.) since it also can often be hit more brutally by the treatments.
Anyway, since many in my family have died from this horrible cancer, its fantastic news to hear of any improvements there.
Sorry, it does not apply ... this drug inhibits (for the first time) the KRAS mutation (previously considered "undruggable") that is the primary cause of 90% of pancreatic cancers and 50% of colon cancers.
Lymphoma is a bit of an outlier. In the case of lymphoma, more aggressive types indeed respond better to treatment, and given that we are now fairly good at treating lymphoma, that translates to good outcomes.
Not hyperbolic, just incomplete ... this drug inhibits the KRAS mutation that is the "master switch" for 90% of pancreatic cancers and 50% of colon cancers. KRAS was considered "undruggable" so this is a huge breakthrough which is why oncologists gave a standing ovation for nearly a minute in the middle of a talk, with some of them in tears.
Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner.
One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position.
This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that target KRAS in cancer, but for decades it's always been thought of as 'undruggable' because of the difficulty of finding any molecules that would affect it.
This new drug, that finally treats KRAS mutated cancers, goes about it in a new way. Instead of trying to gum up the works of a single protein by sticking a small chemical in it, it effectively "glues" the KRAS protein to another protein, CypA, which keeps the switch away from reaching the normal areas where it's "on switch" activity works.
So this new drug means two things: 1) a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, 2) there's an entire new class of drug activity that everybody is chasing at this very moment, so in 5-25 years we'll likely have a huge number more of these sorts of treatments.
How does it avoid targeting KRAS in healthy cells? Or is this another form of chemotherapy where we're trying our hardest to deliver the right amount of poison that kills the cancer before it kills the rest of you?
It doesn't. Cancerous cells have a much higher dependency on RAS signaling to survive, so it's a drug that kills everything that's replicating via RAS signaling, much like standard chemotherapy kills cells in general that are reproducing more quickly.
However this is just the first version of the drug, it can be combined with other modalities to allow more selective targeting of cancer versus not cancer cells (e.g antibody-drug conjugation). And when used in earlier stage cancers, rather than the advanced cancers in this first clinical trial, there's the possibility of lower dosing that has less strong side effects.
This is just the first attack that has ever broken through to hit a key weakness of some cancers. It's the start of learning, a breakthrough that will launch refinements, enhancements, and a ton of innovation. That sort of innovation is sometimes derided as "me-too" drugs, and not meaningful, but some of the biggest advancements in cancer care have been from taking very hard to tolerate treatments and making them more tolerable and refined and better for patients, allowing longer and more thorough killing of cancer cells. I would expect we will see a lot of that here, as well as work towards combinations with other drugs.
This drug targets cells with a KRAS mutation that locks the KRAS switch in the ON state, driving uncontrolled growth. Cells with this mutation are abnormal and predisposed to becoming cancer ... so by definition are not healthy.
>a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for,
Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?
The next 1-5 years will tell us which cancers this new drug will work well on, right now it's only been tried in pancreatic cancer when people have failed their first treatment. The new drug from the article, daroxonrasib, has nine trials i see currently, here:
The first two are the trial that just completed and showed success: people that have pancreatic cancer that failed other treatments, then a "trial" that is meant to give quick access to more people now that it's been shown to work.
Then there's a trial for using it as the first-line treatment for pancreatic cancer, one for lung cancer (NSCLC), and also various combinations with other drugs. I expect we'll see a ton of new trials registered in the coming year. Especially something in combination with colon cancer, because a common drug resistance mechanism in colon cancer is to develop KRAS mutation.
The thing is that we don't really know which cancers it will work well in until we try. And there's limited number of people with cancer that enter clinical trials, and we want to give each person their very best chance at survival, and then there's the massive expense of running the clinical trial itself, so learning happens slowly, one month of survival at a time, or one cancer recurrence at a time, or one death at a time. Patients that take part in clinical trials really are the heroes here. (Especially with the side effects of this new drug, which are horrible. It is a revolutionary drug, but we need to learn how to manage the other things it does as well, and that's going to take time.)
But that's not a cure. If they don't take that drug, assuming it works, they still have the original mutation in the cancer cells.
> Patients that take part in clinical trials really are the heroes here.
Are they?
To me personally, putting people into a permanent state of requiring drugs to survive, is not really cure. It's just maximizing income for those selling those drugs. And none of those drugs work exceedingly well; people still die, even if to other disease or frailties. I don't understand this hype in general.
I think the meaning is that because we can see success with KRAS mutation of pancreatic cancer, we can now begin clinical trials for other cancers that may have KRAS mutation (colorectal, lung) and see if there is success there. If there is success in treating other cancers during clinical trials, it could be fast tracked through FDA to be more generally available and then become part of the national treatment option (ideally in 1-5 years after clinical trials).
The golden panacea for this would be a gene editing mechanism that will work in every cell in the body. Once we have something we can do whole hog gene replacement, most human health problems would be solved forever.
For every cell mechanism that's being abused by cancer to fuel its growth, there are other cells in the body for which that mechanism is crucial for their correct functioning. Wholesale editing every cell in the body mostly guarantees that the patient does not die of cancer -- the cure will kill them before the disease does.
Yes, and one of the hallmarks of cancer is a removal of the usual DNA damage checkpoints. Cells have sensors that detect damaged DNA and stop cell division, and once that is gone evolution happens on an extremely accelerated times scale. In lung cancer, for example, we have developed entire series of drugs to go after successive resistance mutations inside the EGFR gene.
When we first started getting good at sequencing the DNA of tumors, I remember initial reports of taking samples across the 3D space of a tumor and finding great spatial heterogeneity in the tumor genomes.
I'm actually most excited for using this drug in combination with colon cancer, where KRAS mutation is a common drug resistance evolution in response to drugs that target the gene EFGR (though cancer researchers may all have their favorites to go after, colon cancer went after my family especially hard).
Absolutely, this is selective pressure at work on cells with malregulated genetics. Most typically, this is in the form of drug efflux pumps, but you can definitely get more specific resistances.
Ways to avoid specific resistance include multiple treatments simultaneously, since the probability of generating resistance to both is the product of the probability of resistance either.
evolution is a wrong concept to approach it. cancer is not a separate life form, but a bug in the regeneration system of a complicated life form. it doesn’t exist outside of it, it cannot propagate.
Cancer researchers generally refer to it as evolution, and I've never heard any complaints from the population geneticists or evo-devo folks about it, so I don't think it's a tremendously controversial way to talk about it. See for example
I know this is a popular "well actually" to do, but it is not always useful in a conversation. Yes, all cancers are different, but yes, cancer is also one thing: unchecked, harmful division of cells.
Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once. It is reasonable to talk about bacteria and antibacterial medications, it is also reasonable to talk about cancer and cancer treatment. I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).
It seems relevant here because the question was “How will this potentially help me if I get cancer?” and the answer is “Not at all unless you get a particular form of cancer that this applies to”.
> Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once.
Except people don’t ask “what if I get bacteria” the way they ask about cancer. If the story was about a new antibiotic that only affected 20% of common infectious bacteria strains and someone asked “in laypersons terms, how will this help me if I get a bacterial infection”, it would be appropriate to clarify that it only applies to some bacteria.
> Except people don’t ask “what if I get bacteria” the way they ask about cancer.
Yeah, but doctors also don't tell people "you have bacteria" or claim "we found a cure for bacteria". The lack of nuance on average is largely due to a lack of nuance from experts. The media treats cancer as one big thing and bacteria and viruses as separate things. Thus the average joe inherits 'treating cancer as one big thing' from the media.
I understand where you are coming from here, but I think it is helpful for people to overtly grasp that there are very different cancers, very different treatments, and indeed very different outcomes.
Without this understanding it becomes a quick jump from "we're spending all this money on cancer" to "we've made no progress"
An example of the nuance plays out in the common cancers (like breast and prostrate). These have between 90 and 100% 5 year survival rates. Others (like the one in this article, pancreatic) have very poor survivability.
As you note, it's very unlikely that we'll "cure cancer". But we already "cure" (for some definition of cure) some cancers. Progress is slow, methodical, and incremental. It can feel like a lost cause when viewed from afar, but up close very real progress is being made. And that's an important message to pass along.
The other part that is simply missing is that cancer, very unfortunately, evolves and mutates. That's how you go from a cancer that responds to treatment to one that is treatment resistant.
Like you said, for a lot of common cancers we have multiple treatments. It's usually not just one magic drug, but rather the doctors working with the most effective treatments down to the least effective treatments.
Depressing: evolution has discovered a universal cure for cancer, and it's reproduction. You make a whole new human without the bad bits. Other humans have to evaluate which bits are bad.
> We have penicilin that works against all human cells.
Penicillin works against bacteria, in particular gram-positive bacteria; to a lesser extent gram-negative bacteria too (this depends on the cell membrane structure of bacteria; there are other penicillin derivatives that are also more effective on gram-negative bacteria than penicillin is, but by and large the main target will be gram-positive bacteria). It does not work against human cells. If your comparison is about drugs in general, then of course cytotoxic drugs will have an effect; simplest example I can remember off-hand is colchicin. Of course it should work against cancer cells and non-cancer cells, unless there are some mutations where colchicin could no longer bind to, but that seems very very rare, due to the natural target of colchicin involved in cellular division.
Cancer cells, by definition, are not a uniform mass. It will depend on the cancer type, which in turn is defined by the properties those cells have. And mutations happen all the time, often more in cancer cells when their repair systems also have mutations, e. g. are less efficient. By that definition alone, there can never be a wonder-cure for all cancer types. At best you can find some proteins more important (p53 for instance) and while more than 50% of cancer cells have some form of mutation in p53, others simply don't. By that definition there will never be a penicillin-equivalent to all cancer types.
The correct way to read the sentence is “all cancers do not have the same causal mechanism” but people don’t talk like that because it’s off putting. Language is fluid and it’s generally on the reader to infer meaning from context. If we can do so reasonably, we do it, and we don’t need to then write additional posts chiding people over an interpretation that’s highly unlikely to be the intended one. I don’t mean to be pushy about this, btw. It’s just that pedantry can be valuable, but only if it isn’t abused.
It won't help... mind you this is an article from the economist. There is no such thing as a cancer "master switch", that would equal a disease master switch and that point we have solved biology.
There was a KRAS conference a couple of weeks ago, and as I understand it that's exactly what happened. It is such a game changer that they could not contain their excitement. For all the ridiculous talk of "they're being paid by 'Big Pharma' to prolong treatment to make them money", I assure you that oncologists DEEPLY want to become "obsolete". They want a cure. They want patients to live. Drugs like this and many others on the horizon are another step in that process.