Treating pancreatic tumours may have revealed cancer's master switch
economist.comThat said, I'll happily take "we discovered a key weakness in 20% of cancers," please and thank you.
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.
Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?
https://clinicaltrials.gov/search?intr=daraxonrasib&viewType...
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.)
> 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.
> 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.
The person you're replying to called this out specifically:
> and also various combinations with other drugs.
Why do you think they try it in combination with other drugs? You might be right that this drug alone might not be a cure, but if it inhibits cancer growth, then it empowers other drugs to work more effectively.
> people still die
So what... We do nothing, then? This is your complaint? That we can't be immortal, so why bother trying to cure anything?
I don't understand your type in general.
https://usafacts.org/articles/how-have-cancer-rates-changed-...
>However, even though the overall number of cases rises as the population grows, fewer people are getting and dying from cancer. Between 2000 and 2021, the incidence rate — or the rate of new cancer cases per 100,000 people — declined by 5.7%, while the annual mortality rate fell by 27.5%.
Cancer is a broad term encompassing many sorts of malfunction and nearly 40% of Americans will be diagnosed with it at some point because if you survive other hazards and maladies cancer is often what gets you.
The pharmaceutical companies are not the ones making clinical decisions - in this case, it's a shared medical decision between a patient and their oncologist.
Having seen how horrific pancreatic cancer is, how difficult it is to treat, and the decades of slow research done by academic scientists to get to this point, I am elated that we have a tool to give patients more time with their families even if their cancer can't be "cured" with this particular drug. This may seem unsatisfying, but it's real, measurable progress. It also opens the door to new drugs in the same class that could be even more effective.
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).
> 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.
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.
But yeah, oncologists aren’t telling people “you have cancer” the way they might say “you have MRSA”.
Honestly, I think people probably get false impressions because cancer usually hits old people and old people are, frankly, often not reliable narrators.
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.
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.
Now, "no, i mean poisons that attack the special chemistry of cancer," oh yes, those we call chemo.
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.
Penicillin blocks a specific enzyme (transpeptidase).
https://en.wikipedia.org/wiki/Penicillin-binding_proteins
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.
It most likely will help if you get pancreatic cancer. It might help if you get one of the other types of cancers with this mutation.
And it will likely lead to new treatments for some of the worst kinds of cancer.
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.
Prove it. Prove this happens at a large scale. This is just nonsense talking points.
I'm sure the average person was completely fed up with the federal grant process for medical issues and it was a driving force in their voting decision. Excellent proof.
There is no leftist scurge I'm science.
I doubt "10s of millions of Americans" can describe the core functions of the NIH
> when scientists are hired because they know someone, or are part of some “group” rather than being the best choice.
How do you think new appointees and hires in the NIH/HHS are selected? Political loyalty seems to be a better predictor than scientific impact or output.
> Also not interested in funding anything not research related, including various “offices” that have nothing to do with supporting research. Lots of things to like about these cuts.
The cuts and changes are dramatically impacting research support. Grant money is not being disbursed at the same rate since the new review changes began. You can more plainly characterize the changes as harmful to research in general than focused on removing whatever specific things you don't like.
It makes no sense to cut off the hand that saves you even as a rich billionaire who wants to control people in a fascist society.
In reality, mediocre thinkers with inflated egos and little understanding of long-term consequences are pulling the strings almost everywhere.
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.
Baby steps.
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!
The patient's metastasis markers were so high the value was literally off of the maximum value on the graph on the chart they gave us in the literature, and so, well beyond the level of being surgery eligible.
Over the 12 chemo cycles that number dropped to levels that cancer free people have, and they have gone on to outlive almost every statistic and remain cancer free to this day.
When researching pancreatic cancer following their diagnosis one thing that stood out to me is how the majority of scientific knowledge surrounding cancer addresses the cancer's metabolism. Pancreatic cancer is an IGF-1 (Insulin Growth Factor) metabolic cancer. This can be interpreted as the cancer uses sugar as its fuel source to grow, and in the absence of sugar can alter its internal metabolism to use an amino acid called glutamine as fuel instead. Glutamine is an amino acid found in animal products such as meat and dairy.
With this knowledge we went with a food regiment of removing ALL sugar, and animal products.
The results were significant. Even in their 70s they were able to do the full 12 cycle chemo treatment without needing to delay a single cycle due to negative health markers, and without any major side effects (except fatigue).
The tumor shrunk form 4.2 cm to 2 cm after 6 chemo treatments, and finally shrunk to 1 cm following their final treatment before surgery. (Compare this to studies on tumor shrinkage for the same cancer and chemo treatment, such as: https://www.healio.com/news/gastroenterology/20210722/early-... )
It is my opinion that at this time medical treatment is essential, both chemo and surgical intervention, but if you want something that you can do to try to increase the efficacy of those treatments I highly recommend this nutritional vector as well!
Best wishes for you and your loved ones.
They slacked a bit some months following the surgery, and their blood markers started to drastically slip almost immediately.
Might be also worth noting that prior to all of this they were a staunch "antivegan midwestern farm boy" for 70 years.
Now, after witnessing the results, they are all in on the new dietary lifestyle change, and tell all their friends.
It's 2026, this is SOP.
It's why I referenced the metabolic pathways derived from data backed research, linked to a data driven study, and used language like "we had significant success with our loved one" and "if you want something that you can do to try".
Honestly this reads like an "aHCkTualLy!1!" from someone without experience of having a loved one suffering from a cancer diagnosis.
Perhaps you've yet to realize but shallow skepticism against every idea is also distinct from data.
While you chose make this comment without providing links or data to support your claim I will do the real work of finding even more data for you: https://www.sciencedirect.com/science/article/pii/S000291652...
Anyway, my point is, don't worry too much about the ignorant "but actually" replies here. There's probably been thousands of people who've read your comments and only two felt the need to make these retorts. The others most likely in the majority felt your comment had merit.
This is very true. It was certainly a lot of work for us, and a lot of work for them.
In the first months I was cooking everything.
By the end of the chemo treatment the patient had learned to cook these new meals for themselves.
But since we don't actually know whether such a recommendation will harm or help any individual patient, no one should be taking this recommendation as advice, and at the very least you should not be "highly recommending" specific dietary changes to people based on one anecdotal experience.
We made sure to still cover all nutritional needs while following the diet.
This meant a diverse array of food sources, in sufficient amounts to meet micro and macro nutrient recommended daily values, that we cooked ourselves.
Also, sugar is essential to what makes you you, that is, the brain requires glucose to function.
The goal is to reduce excess intake of these things to reduce their availability for any cancer cells to use to grow and divide.