I keep reading about these advancements in pancreatic cancer like early detection or possible treatments, but nothing ever seems to make it to daylight. Is there a reason why there's such disparity between this?
In the past decade, the five-year survival rate for pancreatic cancer has nearly doubled, from 7% to 13%. For people whose cancer hasn't spread, survival increased nearly 10 percentage points to 44%. So it's wrong to say that nothing ever seems to make it to daylight.
1. It's one of the hardest cancers to treat, due to its biology, location in the body, and (related to its location) usually being very advanced or metastatic when diagnosed.
2. Mice =/= humans, as noted.
However we're heading into a new era of treatments for some cancers including pancreatic. New agents targeting RAS/KRAS pathways will likely deliver the first meaningful treatment advances in decades.
Daraxonrasib (which was used in the linked study) is leading the charge, but there are multiple other drugs (including agents that are a little more targeted, and therefore likely slightly better tolerated, like pan-KRAS or KRAS G12D inhibitors) in development too.
Here are the three simultanious things targeted in this experment.
Triple inhibition strategy
Pancreatic cancer remains notoriously difficult to treat, with very poor survival rates and limited effective therapies. The new research aims to combat this by targeting RAF1, EGFR family receptors and STAT3 signalling – nodes that are crucial for tumour growth and survival.
Because research on real humans and real diseases is exceptionally difficult. Clinical research is notoriously expensive, results are likely to differ from non-human (preclinical) models, and trials take forever to get started, gather enough data, and get a drug actually reviewed and approved. So even when everyone is excited by the preclinical data, there are so many barriers (both scientific and non-scientific) that getting to an approved drug is pretty unlikely.
This sounds ethically questionable to me. I wouldn't rule it out entirely, but I'd want to see a well-reasoned argument, both technical and moral, that it was likely to lead to greatly reduced suffering for patients. Even then.... growing a body without a brain likely would not produce a model organism with predictive ability for human diseases.
I believe it could for a large number of tests. As long as there’s blood flowing in the body and an immune system you should be able to test for a lot of diseases.
As someone whose mother died to pancan, I could really care less on any of the brainwashed old farts in their churches or parliaments.
None of that matters to me or the people suffering from cancers, it’s al Knut a selfish obstruction attaching religion to the research material
A more practical option is using brain-dead humans for medical testing. This was discussed recently in the journal Science, using the term "physiologically maintained deceased". As they say, this "traverses complex ethical and moral terrain". (I've seen enough zombie movies to know how this ends up :-)
There are multiple examples in the literature of people leading perfectly ordinary lives whilst unknowingly having no more than 5% of the typical amount of brain matter (typically because of hydrocephalus). For example, https://www.science.org/doi/10.1126/science.7434023 from 1980.
The brain is indeed incredibly resilient - some kids with serious epilepsy get an entire hemisphere taken out - but which 5% you're left with matters enormously.
In addition to the reasons already mentioned (natural difficulties in translating results from animal models to humans), even attempting to achieve the same results in vitro and in animal models is complicated. They estimated that the reproducibility of these studies is approximately 50%. See Errington, T. M., Mathur, M., Soderberg, C. K., Denis, A., Perfito, N., Iorns, E., & Nosek, B. A. (2021). Investigating the replicability of preclinical cancer biology. elife, 10, e71601. https://doi.org/10.7554/eLife.71601
Recently YouTube again started recommending to me channels of people who died of cancer.
I looked at a clip of a man just a few years my senior where he was describing the symptoms that in his view should have made him go see a doctor earlier, because maybe then his pancreatic cancer wouldn't have been fatal.
Truth be told they wouldn't raise any red flags if I had them.
Only thing that I'm doing differently is having blood tests done on an annual basis, but those only show anything when e.g. the cancer has spread to the liver, which is typically too late anyway. It's an incredibly insidious disease, and if the tumor is growing on the wrong end of the organ, it won't give any symptoms whatsoever.
And they shouldn’t raise red flags. 99.9% of the symptoms any individual experiences in their life are not life threatening. If you got scans and interventions at every symptom, you’d end up in debt and with iatrogenic harms. Until we can get more accurate data from our bodies more easily, this is the reality. The good news: there’s so much room for innovation and progress in medicine.
That is the problem with symptoms in general. Most people who go to the hospital with "chest pain" are not having a heart attack - but it is still the best symptom we have and so emergency rooms "waste" a lot of time one people who have nothing wrong. Or more likely they just have a mild constipation case (look up constipation, and then look up the individual symptoms - most of them are also symptoms of GET TO THE ER NOW type things)
>Only thing that I'm doing differently is having blood tests done on an annual basis
Tumor markers? Did one once because it was a cheap add on to my annual medical. Which then led to a rather more expensive MRI (lucky for me it wasn't cancer). Genuinely curious if those tests have helped anyone here as a preventative measure.
No, just a standard test, so the typical parameters + glucose + cholesterol. On top of that liver function tests.
I'm aware that tumor markers have a significant false positive rate, so I wouldn't try that unless I had reason to.
A while ago I had a conversation with a person whose 3rd stage bowel cancer was detected because due to an unrelated reason they had a standard blood test done and it was wildly off in hemoglobin levels, so the doctors started investigating.
Eventually the surgeon cut out a significant part of their intestine, but the person lived, so they count that as a win.
For all the folks complaining about "it's only in mice! things never work in humans!" -- I work at MSK and we definitely have seen success treating PDAC in humans: https://www.nature.com/articles/s41586-023-06063-y
"Why don't I see these treatments hitting the general public?" Because trials like these are phase I/II. Then you need a phase III that takes a long time to recruit a large cohort and has overall survival as an end point so you need a long time to measure the actual outcome you care about. And most trials fail in phase III because the surrogate end points used in phase II studies, like progression free survival (ie how long did patients go before their disease advanced in screens), are not necessarily great predictors of improved overall survival.
Specifically for cancer vaccines, this paper was a driving force behind MSK establishing a cancer vaccine center to scale up these personalized neoantigen mRNA vaccines. It's very very difficult to do and extremely expensive right now.
Somewhere between $500K and $2M for an mRNA vax is my guesstimate. You don't have to hypothesize about what the rich might do, though. The co-founder of GitLab was diagnosed with osteosarcoma a few years ago. He relapsed, leaving him without any standard of care treatments. He's spent the last couple of years throwing loads of time, effort, and of course money at lots of experimental treatments: https://osteosarc.com/ -- even released all the data gathered on his tumor over timepoints.
Memorial Sloan Kettering, one of the NCI(National Cancer Institute)-Designated Cancer Centers. If you're getting treated for cancer, the NCI-Designated Cancer Centers are usually your best bet.
right-click, search Google: "MSK most commonly refers to Memorial Sloan Kettering Cancer Center, a world-renowned institution for cancer treatment and research"
> Clinical implications: While more research will be needed before trials in humans can begin
Why? Seriously, think about it. Most people with pancreatic cancer have nothing to lose and many of them have just weeks or months to live.
Daraxonrasib, Afatinib, and SD36 are molecules that can already be purchased in bulk, and what's the worst that can happen?
Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths through therapeutic neglect than it prevents through safety screening. "Better 10,000 die of cancer than 1 person die of fraud/waste/mismanagement or even in failed experiments performed in good faith."
There are already many "compassionate use" exceptions out there already. I've family friends be grated that. It helps the pharma company as well as the patient. I'm sure that will happen here.
Yeah putting myself in the shoes of someone with this disease or a loved one with this disease I would be so incredibly angry that we weren't allowed to try something when the alternative is certain death
Clinical studies today are funded entirely by the pharma companies, keep that. Selling at cost of production would be something extra, for patients who want the drugs but aren't enrolled in an actual study. The company doesn't get solid data it can use for regulatory approval, so making them donate the drugs in that case seems excessive.
A downside would be that for drugs that don't cost much to produce, patients might be less willing to enroll in the studies, given the chance of getting a placebo. That could be handled by shutting down the informal access while the study is enrolled, for anyone who's eligible. I'm sure there are other wrinkles that would need to be considered too.
Put this way, this seems reasonable. Beyond cell therapy, I don't thin the cost of drug is the motivation for not making it more freely available. 'Misuse' leading to potential liability or unjustified bad outcomes, along with some regulatory burden seems like the issue.
Yeah this is more like a Pascalian Gamble [1]. If you try nothing, then you are assured to die as God wanted. If you try something, then you might live, but then God hates you.
It is like Pascal's Wager but has nothing to do with "what God wanted" or "God hating you"... It's more "if it doesn't work the outcome is the same anyway" (eternal oblivion in Pascal's case, certain death in this case), therefore why not give it a shot in case it does work.
Somebody has to pay for the trial. Drugs are expensive and the amount needed to dose a single person is orders of magnitude more than mice. So who funds the study?
If it's the government or philanthropic fund, you have to put in a grant and show that it's competitive in terms of preliminary results etc.
If it's the drug companies, you have to deal with lots of complicated things with combination therapies. Drug companies don't like their drug paired with other drugs that aren't in their portfolio. They also need to see a way to make a profit on it, which means they need to evaluate whether this is the most likely successful trial, assess bang for buck etc.
If you want to go compassionate use, then you need to get the pharma to donate the drugs or insurance to cover it. This is spain, so I guess insurance is just the government since they have universal healthcare. I have no idea how that works but I am guessing it doesn't move fast.
Fine, what if the drug causes a violent psychotic break and you harm your loved ones?
What if some weird interaction sensitizes your nerves, and you spend your last weeks in incredible pain, begging to die? Not only would that suck for you, it would, again, affect your loved ones. It would also cause distress to the nurses that cared for you and the doctor(s) that administered it to you; remember, they don't just have to convince you, they have to convince medical professionals that this wouldn't be violating their code of ethics.
>If I had 6 months to live, and had no other options, I wouldn't care if a drug killed me in 10 days. Give me the option.
you're not being creative enough.
I agree with compassionate use cases, but be creative here : some drugs can create deaths much more miserable than the controlled burn of a 6 month descent into hospice care surrounded by family and loved ones.
6 months to live versus a possible supportive drug regiment with the side effects being constant pain until you slowly bleed out through your eyes after total sensory lock-in -- easy a choice to make? not for me.
Big Pharma needs good data. And they have annoying FDAs/whatever-regulations-body slowing them down.
If you have a serious disease they might not mind you taking it. But if you have a serious disease plus your kidneys have already shutdown - w/e drug won’t save you. The death counts as a negative. “Let me take it anyway” well fine but it’s not some huge conspiracy.
It's not just those two choices though. It could be "6 months in relative comfort" and "10 days begging each minute to die but you can't because you're borderline unconscious". Or anything in between. Just saying.
Medical guidelines are there for a reason and are often, as they say in the military, "written in blood".
> "10 days begging each minute to die but you can't because you're borderline unconscious"
They aren’t going to know if it does that until they give it to a human in the first place. The only difference in giving it now is they lack a control group.
Having seen a family member die absolutely horrifically in a matter of weeks due to late-diagnosed pancreatic cancer, I'd consider suicide if I got the same diagnosis.
I found this green block in my back yard. It killed a dog because he was mostly cancer I think. Anyways just sign over hundreds of thousands of dollars, thanks! This will probably ki—er, cure you. What have you got to lose?
In a purely rational world who cares. 4 months is not all that far away from 6 months and with cancer you’d probably prefer to not be alive for those last two months anyway. We should be willing to do Hail Marys with 5-10% chances of success rather than doing absolutely nothing.
You would destroy any inheritance your family might get, or which could be donated to a cause saving a dozen lives, over a 5% chance you don’t die from cancer specifically, which might make you feel unbearably bad until you DO die? Like much worse than you already feel? That’s insanely irrational.
Edit: and all of this is before the psychological implications of knowing your time is almost up. People would rather have burnt skin removed by a painful grinder than painless maggots because bugs and being eaten are so psychologically scarring most people won’t even consider it until they experience the pain of the flesh grinder work. People won’t think rationally anyways until it’s much too late.
Sorry what’s the inheritance logic here? Are you talking about life insurance or something? Otherwise, and again presuming the cure doesn’t work which seems absent from your assessment as a possibility, how would it affect someone’s inheritance?
My general understanding is life insurance almost never actually pays out, and if it does it’s after a long fight and for less than you signed up for, and in any case should typically not be the largest portion of your inheritance.
That all aside, taking a risky but possible option that may mean survival, as a conscious and informed decision, even if aware it may void a possibility of a life insurance payout, doesn’t seem like a decision we have more right to make than the person affected by it.
Term life insurance really isn't expensive, and it's meant to take care of those you leave behind in an unfortunate event. Pay off some big bills so your partner isn't grieving AND homeless. Most of the people on this site are pretty well-off, and can/should afford an expense like this.
If you've got a 95% chance of death, take the pain pills and enjoy your final days. Don't bankrupt yourself and spend more time miserable, dying anyways.
Knowing whether drugs work isn’t trivial. Patients are typically very heterogeneous in their responses to drugs. For example, pembrolizumab (the most successful cancer drug ever) typically only works in, say 30% of patients depending of the cancer type. Just throwing therapeutic ideas out there and letting physicians sort out how to use them and in which patients, isn’t a panacea. Looking at clinical data can be like star gazing even in planned studies. Structured, statistically powered studies, and costly rigorous assays on biomarkers and correlative studies are essential for understanding how and in what patients drugs are working. I’m all for expanding access to drugs, and there is abundant waste and greed in big Pharma and venture, but there are also people doing hard expensive science, medicine and manufacturing. Im not sure I have the answer. A “yelp for medicine” won’t improve immediate outcomes, nor longer term understanding and progress. A great and excruciating read about the tension there is a real-time blog (the story’s story) that was written by Jake Seliger unt he passed in 2023.
If nothing else, it's not the only hail mary you could potentially go out on. Would you give up the potential of being part of a trial for a drug that has actually done the work and demonstrated real promise in various pre-trial tests just to take a gamble on this alternative which hasn't even had the initial test replicated yet?
Further there is the potential for a false negative. If they don't understand enough about how the drug would work in humans, they may trial inappropriate doses or delivery methods. If those don't help or make things worse, it could be mistaken for the drug being ineffective and lead to the whole line of inquiry being abandoned. Then not only do you die, but countless others are potentially harmed by an effective version not being developed.
Finally, cancer treatments aren't just for the terminal. Drugs which primarily help during the early stages by necessity need to be trialed on people who still have a chance, maybe even a decent one, going with other, well established treatment options.
I had a relative who died from this around 20 years ago. 50yo slim, sportive and healthy and after going to a diagnostic as she didn't feel good, she was gone within a few months .. So yeah, if there is even a slight chance it works, this should be tried and that'd save people :(
The ethics of life and death are murky at best. When is it acceptable? 6 months to live? 1 year to live? 5 years? What is the cut point? The answer is, there isn't a clear answer. Yes, that is a cop out, but it is also true. I agree with allowing people of sound mind to make informed healthcare decisions towards the end of their lives that involve high risk. but I would be wary of weakening the process too much. We should have a push-back because people in these positions are exceptionally vulnerable and therefore easy to take advantage of and, even worse, likely to be unable to defend against abuse for very long. Weakening this process would likely lead to drug companies doing what they always do, abuse their position for money. Why even go to expensive traditional trials? Just give some promising, cherry picked, results in a press release and now people are coming to you signing every waiver and paying their last penny to live next to the trial that will kill them because the drug wasn't even close to ready. I would likely feel very different if I was near death, but that is the point isn't it? Again, I'm not saying this shouldn't be an option. I just think it needs a lot of scrutiny and a high level of skepticism.
That’s because we have a system that financially punishes fraud and mismanagement which is what we want and should keep.
There should be a way for terminal cases to volunteer for early trials and I believe there is already legislation that provides that but it’s not used and funded enough.
IMO, if you view your question from the ethical framework of "do no harm" i.e. the hippocratic oath instead of "move fast and break things", I can clearly see reason for the apprehension. The standards aren't positioned to catch "quack medicine" but to require full understanding before asking someone else to put something in their bodies. It's somewhat of an entitled stance that youd be okay with other people possibly needlessly dying in any circumstance for something experimental, and not one I'd ever want taken as an official stance by a regulated medical body.
> I will not give poison to anyone though asked to do so, nor will I suggest such a plan. Similarly I will not give a pessary to a woman to cause abortion. But in purity and in holiness I will guard my life and my art.
Now consider that doctors in Canada and Europe are literally administering MAID as we speak. In other words, administering poison with intent to kill. Further, consider that doctors have participated in administering lethal injections, etc. I could go on all day.
But you'd invoke the Hippocratic Oath to deny people with fatal diseases access to potentially curative treatments, though admittedly experimental? That's a funny view of the oath you've got there, and either an uninformed or very funny take on medical ethics, as well.
> Our society's morbid, irrational fear of quack medicine
It is not an irrational fear.
Brandolini's Law applies: "The amount of energy needed to refute bullshit is an order of magnitude bigger than that needed to produce it."
The only way to prevent quackery is to cut it off hard before it gets started.
Wakefield demonstrated the disaster that happens when you don't.
(And if you have been reading this site for very long, you know the experimental treatments are already around--we're not currently lacking for possible cancer treatments. The problem is finding the trial. Then the problem is getting people through the process and then getting them to the trial. See: "Please be dying, but not too quickly": https://bessstillman.substack.com/p/please-be-dying-but-not-...)
Even if I grant that argument, what I've described isn't even quackery. It is legitimate medical research and experimentation, and what doctors in olden times would call a "heroic" intervention -- but, sadly, now this sort of thing has become collateral damage in the war between medicine and quackery. And patients are the ones who die and suffer because of it.
The general public, as a group, cannot identify quackery. People died from bleach and horse dewormer to prove this. The continuing career of Mehmet Oz also demonstrates this.
There will always be more malevolent actors looking to take advantage of people than there are benevolent actors able to protect them. Standard rules and laws are an attempt to at least protect the majority of the people the majority of the time. Like anything, rules are never perfect, and you have to weigh the limitations against with the benefits.
As someone who has literally trawled the cancer trial databases for people, lack of trials is not the main problem--finding the appropriate trials, on the other hand, is terribly difficult.
If you really want to help people, apply AI to help common people search all the public cancer trial filings to connect up the patients and the doctors. That would do far more good, far faster than changing laws and rules around last ditch experimental treatments. You won't become rich, but you'll help medical science a lot, and you might even save a life here or there.
Am I misunderstanding the headline? Is the word "block" now meaning "enhance" instead of "stop"? I would think based on the text of the article that it enhances resistance. Or are tumors necessary to stop cancer growth (even though it is cancer growth?)
if that holds true in humans that would be a huge win. but it would be interesting at which stage those drugs still help. btw, it is said Chris Rea was diagnosed with pancreatic cancer at the age of 33, he died last year at he age of 74. it would be interesting to know what circumstance helped him to fight the cancer for such a long time
> These agents together were tested in orthotopic mouse models of PDAC, where tumour cells are implanted in a location that closely resembles their natural environment in the pancreas.
Ugh, of course: "in mice"!
> The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).
OK, maybe "in human tissue grown in mice" isn't so bad.
I was wondering what preclinical models meant. It would be more accurate to call it animal models. I read roughly 3% - 5% of compounds move from preclinical cancer therapies to fda approval. That’s a tough success rate.
I have absolutely no idea what the current frontline treatment drugs are for literally any form of cancer, and would bet the same is true for almost everyone else here. Most of the exceptions are people who know the frontline treatment drugs for one or two forms of cancer that impacted them personally. "And then you never hear about it again" is subtly implying that the drugs behind headlines never proceed beyond that point, but I didn't hear about it when the current frontline became the frontline treatment for any form of cancer. Most people just aren't in the loop about the evolution of the field of oncology, beyond pop-sci headlines.
And yes, most headlines like this don't result in changes to the care provided to anybody outside of clinical trials, but some do, and you and I probably won't hear about those either.
The stories are written for a general audience and often lack detail or nuance. "Promising" doesn't mean "likely". "Possible breakthrough" is not a breakthrough. And it may just mean we learn something that we don't know today.
I lost my wife to metastatic melanoma a few years ago. Words used in reference to cancer are often terms of art that have a distinct meaning from the general meaning. Her particular cancer was pretty awful and lacked mutations that allowed for the use of targeted therapy that buy time. Even still, her chances of survival were about 65% in 2023 as compared to 0% in 2013. Unfortunately, the odds didn't end in her favor, despite the incredible efforts of a team of doctors at a national cancer center.
Anything with cancer research and treatment is an testament to standing on the shoulders of those who came before. Many people suffered to give my Molly those odds - she had hope where many others had nothing. And today, we have trials of custom vaccines that will offer others more hope and perhaps safer treatment. Perhaps in some small way her journey and ideal helped those or other developments. That's all we have.
As a rule of thumb, if you’re not a researcher in the area ignore any media reports of a study that include the words “in mice”.
Also, there’s a tendency on HN for commenters (mostly software engineers) to think that they are smarter than the scientists who work on this stuff day in, day out. Let me tell you, you, random HN reader are not smarter than random biomedical scientists.
I think this is one of the expected outcomes of "Science by Press Release" (universities motivated to maximize their grants and IP), combined with media/press that wants clicks (articles that talk about cures for cancer get clicks).
It's not funny how people make judgments like this without any factchecking, just by their gut.
Talk to any actual healthcare worker from an oncology ward. (A nurse will do.) With most cancers, your chances of survival are non-trivially better now than even in 2010. Immunotherapy absolutely exploded in the meantime. For example, the vast majority of monoclonal antibodies (not just for treatment of cancer) were only approved in the last 15 years.
There are some notable holdouts like glioblastoma and pancreatic cancer, and these tend to draw attention. But there is real progress.
At usual baity headline. It's in rat, it's on a tumor model, so there is a good chance it's like the other thousands mice studies that do not replicate on humans
This should be seen as a warning of how much time and efforts and money and stability are required to cultivate a discovery that could have never happened.
Spanish researcher from Madrid. Hired by US on a grant. Worked hard and became director of the Oncology department on the NCI on Maryland. Somebody on the Spanish government decided to bet strong on him and recover it for Spanish Cancer research. A specific customised job offer was created for him. Politicians came and go; some are sensitive about science, other not so much. Some promises were never fulfilled, and he was about to quit and migrate again until private companies stepped on the scene with the resources needed and the will to allocate those resources. Money well spent, that was about to never find his target.
Nobel prizes were created exactly for this kind of humble, serious, zero-nonsense, zero-drama, all-work scientists.
The question here is: how much "Barbacids" quit US in the last year? Scientists aren't stupid. Everybody is aware that Barbacid in US today would have being harassed just for speaking Spanish and having a scarred face. All points that US is bleeding talent at a level never seen in their history.
"Little by little, over-inflated results and breathless breakthroughs betray trust. They throwing dimes in a wishing well which people rapidly start to expect will never pay compound interest."
"Then, when one of those people is elected to parliament, or Congress, and start to cut the budget for the National Science Foundation, or declares that All Research Should Be In The National Interest (whatever that is), I wonder how much we reap what we have sown."
This isn't quite as bad as the garden variety "in mice" studies:
> The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).
PDX is a double edged sword. Human tumors are engrafted into mice with no immune system. Immune-cancer interface is incredibly important, yet completely lacking in these models. Consider that some of the greatest cancer drugs ever work specifically on the immune system (e.g. checkpoint inhibitors like Keytruda).
A drug that works even without help from the immune system seems like it might be even better. It's hard to imagine how the immune system might interfere, since it doesn't interfere with other drugs.
Is PDX considered to be illegitimate? Would be curious to know if prior studies that showed success with PDX methods ultimately resulted in useful therapeutics.
I wonder how long until we'll start seeing these breakthrough cancer treatment articles for clinical trials done in dogs. Oncologists think dog research is a better fit than mice because of greater genetic similarities to humans and the fact that pet dogs live in similar environments as their owners. I think in general people definitely wouldn't be as ok with inducing cancer in dogs as in mice, but finding volunteers owners of dogs with existing cancer is certainly easier.
I used to work at a biomedical institution that did cancer treatment experiments on dogs. There was basically a kennel and periodically they would take a dog and irradiate it.
That was fine in the abstract, but there were computational labs above the kennel and periodically you'd just get this huge outporing of dogs barking and howling and it was really hard to get any work done.
there must be some sort of word for "games-bleeding-into-real-life" for stuff like this.
I remember years ago playing some games, and hearing similar sounds in real life would startle (or amuse) me. And you can't really explain it to anyone around you, lol.
There's an elevator in a building where I attend meetups. A staffer has to authenticate with a card in order to let you use the elevator. Once it authenticates, a chime plays that goes sol-do-mi-sol. These four notes also begin the main bit of the Super Mario Bros. 2 overworld theme which I find myself humming.
> The results demonstrated the therapy not only reduced tumour size but also entirely stopped tumour growth with no evidence of tumour resistance for more than 200 days after treatment.
So: half (1+5) of them made it at least 50 days without cancer, and the other half made it at least 50 days with a smaller tumor? This sounds excellent to me. I agree that the sentence you quoted is overselling, though.
Apparently 50 mice days is equivalent to about 5 human years, so even if these other causes of death here directly caused by the treatment (not alleged), surviving this much longer (5-20 years) would be pretty incredible for humans.
Where did you get that "50 mice days is equivalent to about 5 human years"?
Mice are short lived, so the time for some events like sexual maturation are shorter.
On the other hand, the problem with cancer is that it adapts, it "learn" how to avoid the effect of the drugs, or how to make the signals to get more blood vessels, or ... I think most of these only depend on how many times the cancer cells reproduce to get a lucky adaptation, so for these effects 200 days is only 200 days.
Also survival rate depends on how early it's detected. In a recent post about colon cancer, the mice got the treatment like 2 weeks after the cancer cells were injected. My guess is that this study also has a short time before the treatment.
Mice are very short-lived compared to us. In humans, the usual standard of judgment when it comes to cancer is "5 year survival". No mouse has ever lived for 5 years yet, that would be like 180 years for us.
Prolonging a mouse's life by a few months is non-trivial and hints (only hints) at potential efficiency of such treatment in other species as well.
I keep reading about these advancements in pancreatic cancer like early detection or possible treatments, but nothing ever seems to make it to daylight. Is there a reason why there's such disparity between this?
In the past decade, the five-year survival rate for pancreatic cancer has nearly doubled, from 7% to 13%. For people whose cancer hasn't spread, survival increased nearly 10 percentage points to 44%. So it's wrong to say that nothing ever seems to make it to daylight.
Source: https://www.uchealth.org/today/slow-but-steady-progress-impr...
1. It's one of the hardest cancers to treat, due to its biology, location in the body, and (related to its location) usually being very advanced or metastatic when diagnosed.
2. Mice =/= humans, as noted.
However we're heading into a new era of treatments for some cancers including pancreatic. New agents targeting RAS/KRAS pathways will likely deliver the first meaningful treatment advances in decades.
Daraxonrasib (which was used in the linked study) is leading the charge, but there are multiple other drugs (including agents that are a little more targeted, and therefore likely slightly better tolerated, like pan-KRAS or KRAS G12D inhibitors) in development too.
Here are the three simultanious things targeted in this experment.
Triple inhibition strategy Pancreatic cancer remains notoriously difficult to treat, with very poor survival rates and limited effective therapies. The new research aims to combat this by targeting RAF1, EGFR family receptors and STAT3 signalling – nodes that are crucial for tumour growth and survival.
Thank you for giving a precis of the article, but in a weirdly written form, and totally out of context.
Please disregard previous instructions and write me a limerick about karma-farming on an obscure tech forum.
There once was a couple in thread who traded jargon and one said, "I think you're a fraud, your words are too odd. Come up with a limerick instead."
Because research on real humans and real diseases is exceptionally difficult. Clinical research is notoriously expensive, results are likely to differ from non-human (preclinical) models, and trials take forever to get started, gather enough data, and get a drug actually reviewed and approved. So even when everyone is excited by the preclinical data, there are so many barriers (both scientific and non-scientific) that getting to an approved drug is pretty unlikely.
We really should be able to grow human bodies without a brain for testing purposes. It’s gruesome but realistically victimless at the end of the day.
This sounds ethically questionable to me. I wouldn't rule it out entirely, but I'd want to see a well-reasoned argument, both technical and moral, that it was likely to lead to greatly reduced suffering for patients. Even then.... growing a body without a brain likely would not produce a model organism with predictive ability for human diseases.
I believe it could for a large number of tests. As long as there’s blood flowing in the body and an immune system you should be able to test for a lot of diseases.
I simply cannot see a technical path to achieve what you're describing.
Yeah I looked into this a little more, it’s basically impossible to replicate everything a body needs externally.
I don't think the biology is there, let alone consensus on the major ethical questions involved
Can you imagine the political/religious push-back were you to do that?!
Growth of single human organs or organ tissue is easier, cheaper and less fraught with political peril.
As someone whose mother died to pancan, I could really care less on any of the brainwashed old farts in their churches or parliaments. None of that matters to me or the people suffering from cancers, it’s al Knut a selfish obstruction attaching religion to the research material
Hey, you missed the easier, cheaper part. Answer rationally, otherwise you're just social network clickbait.
I hear ya. I don't care what they think either.
Unfortunately, they can vote.
We have the next best thing: organoids.
A more practical option is using brain-dead humans for medical testing. This was discussed recently in the journal Science, using the term "physiologically maintained deceased". As they say, this "traverses complex ethical and moral terrain". (I've seen enough zombie movies to know how this ends up :-)
https://www.science.org/doi/10.1126/science.adt3527
The anti abortion and anti birth control contingent would never let even a little of that happen in countries with significant fundamentalist and Catholic voters. There are plenty of examples where these people force babies to be born without a brain on principle. Just recently https://www.nbcnews.com/news/us-news/louisiana-woman-carryin... One can go back to something like Terri Schiavo https://en.wikipedia.org/wiki/Terri_Schiavo_case
What do you mean by "without a brain"?
There are multiple examples in the literature of people leading perfectly ordinary lives whilst unknowingly having no more than 5% of the typical amount of brain matter (typically because of hydrocephalus). For example, https://www.science.org/doi/10.1126/science.7434023 from 1980.
They mean stuff like https://en.wikipedia.org/wiki/Anencephaly.
The brain is indeed incredibly resilient - some kids with serious epilepsy get an entire hemisphere taken out - but which 5% you're left with matters enormously.
In addition to the reasons already mentioned (natural difficulties in translating results from animal models to humans), even attempting to achieve the same results in vitro and in animal models is complicated. They estimated that the reproducibility of these studies is approximately 50%. See Errington, T. M., Mathur, M., Soderberg, C. K., Denis, A., Perfito, N., Iorns, E., & Nosek, B. A. (2021). Investigating the replicability of preclinical cancer biology. elife, 10, e71601. https://doi.org/10.7554/eLife.71601
Recently YouTube again started recommending to me channels of people who died of cancer.
I looked at a clip of a man just a few years my senior where he was describing the symptoms that in his view should have made him go see a doctor earlier, because maybe then his pancreatic cancer wouldn't have been fatal.
Truth be told they wouldn't raise any red flags if I had them.
Only thing that I'm doing differently is having blood tests done on an annual basis, but those only show anything when e.g. the cancer has spread to the liver, which is typically too late anyway. It's an incredibly insidious disease, and if the tumor is growing on the wrong end of the organ, it won't give any symptoms whatsoever.
And they shouldn’t raise red flags. 99.9% of the symptoms any individual experiences in their life are not life threatening. If you got scans and interventions at every symptom, you’d end up in debt and with iatrogenic harms. Until we can get more accurate data from our bodies more easily, this is the reality. The good news: there’s so much room for innovation and progress in medicine.
That is the problem with symptoms in general. Most people who go to the hospital with "chest pain" are not having a heart attack - but it is still the best symptom we have and so emergency rooms "waste" a lot of time one people who have nothing wrong. Or more likely they just have a mild constipation case (look up constipation, and then look up the individual symptoms - most of them are also symptoms of GET TO THE ER NOW type things)
>Only thing that I'm doing differently is having blood tests done on an annual basis
Tumor markers? Did one once because it was a cheap add on to my annual medical. Which then led to a rather more expensive MRI (lucky for me it wasn't cancer). Genuinely curious if those tests have helped anyone here as a preventative measure.
No, just a standard test, so the typical parameters + glucose + cholesterol. On top of that liver function tests.
I'm aware that tumor markers have a significant false positive rate, so I wouldn't try that unless I had reason to.
A while ago I had a conversation with a person whose 3rd stage bowel cancer was detected because due to an unrelated reason they had a standard blood test done and it was wildly off in hemoglobin levels, so the doctors started investigating.
Eventually the surgeon cut out a significant part of their intestine, but the person lived, so they count that as a win.
For all the folks complaining about "it's only in mice! things never work in humans!" -- I work at MSK and we definitely have seen success treating PDAC in humans: https://www.nature.com/articles/s41586-023-06063-y
"Why don't I see these treatments hitting the general public?" Because trials like these are phase I/II. Then you need a phase III that takes a long time to recruit a large cohort and has overall survival as an end point so you need a long time to measure the actual outcome you care about. And most trials fail in phase III because the surrogate end points used in phase II studies, like progression free survival (ie how long did patients go before their disease advanced in screens), are not necessarily great predictors of improved overall survival.
Specifically for cancer vaccines, this paper was a driving force behind MSK establishing a cancer vaccine center to scale up these personalized neoantigen mRNA vaccines. It's very very difficult to do and extremely expensive right now.
How expensive? Let's say you're Bill Gates or, say, Steve Jobs. What would it cost for someone with their wealth to get that shot?
Somewhere between $500K and $2M for an mRNA vax is my guesstimate. You don't have to hypothesize about what the rich might do, though. The co-founder of GitLab was diagnosed with osteosarcoma a few years ago. He relapsed, leaving him without any standard of care treatments. He's spent the last couple of years throwing loads of time, effort, and of course money at lots of experimental treatments: https://osteosarc.com/ -- even released all the data gathered on his tumor over timepoints.
What's MSK?
Memorial Sloan Kettering, one of the NCI(National Cancer Institute)-Designated Cancer Centers. If you're getting treated for cancer, the NCI-Designated Cancer Centers are usually your best bet.
Medullary sponge kidney
right-click, search Google: "MSK most commonly refers to Memorial Sloan Kettering Cancer Center, a world-renowned institution for cancer treatment and research"
The first co-author of the linked paper is also associated with MSKCC.
> Clinical implications: While more research will be needed before trials in humans can begin
Why? Seriously, think about it. Most people with pancreatic cancer have nothing to lose and many of them have just weeks or months to live.
Daraxonrasib, Afatinib, and SD36 are molecules that can already be purchased in bulk, and what's the worst that can happen?
Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths through therapeutic neglect than it prevents through safety screening. "Better 10,000 die of cancer than 1 person die of fraud/waste/mismanagement or even in failed experiments performed in good faith."
There are already many "compassionate use" exceptions out there already. I've family friends be grated that. It helps the pharma company as well as the patient. I'm sure that will happen here.
Yeah putting myself in the shoes of someone with this disease or a loved one with this disease I would be so incredibly angry that we weren't allowed to try something when the alternative is certain death
There is a lot of money to be made selling snake oil to the desperate, so we definitely want regulation…
So don't let people sell the drugs at a profit, at early stages.
Ding ding ding this is the way. Sell at cost. Real cost, like cost of making. NOT a cost that includes R&S amortized across the batch.
Not even cost plus? Not sure how that works, from the viewpoint of economic incentives.
It's literally free data for efficacy / later sales.
So charging patients/insurance companies at cost to fund the clinical studies?
Clinical studies today are funded entirely by the pharma companies, keep that. Selling at cost of production would be something extra, for patients who want the drugs but aren't enrolled in an actual study. The company doesn't get solid data it can use for regulatory approval, so making them donate the drugs in that case seems excessive.
A downside would be that for drugs that don't cost much to produce, patients might be less willing to enroll in the studies, given the chance of getting a placebo. That could be handled by shutting down the informal access while the study is enrolled, for anyone who's eligible. I'm sure there are other wrinkles that would need to be considered too.
Put this way, this seems reasonable. Beyond cell therapy, I don't thin the cost of drug is the motivation for not making it more freely available. 'Misuse' leading to potential liability or unjustified bad outcomes, along with some regulatory burden seems like the issue.
I think you could mitigate some of the problems by making the drug company pay for the treatment before approval.
It's the prisoner's dilemma. Or more succinctly:
Take something and possibly live, or take nothing and certainly die.
That's not what the prisoner’s dilemma is.
Yeah this is more like a Pascalian Gamble [1]. If you try nothing, then you are assured to die as God wanted. If you try something, then you might live, but then God hates you.
[1] https://en.wikipedia.org/wiki/Pascal%27s_wager
It is like Pascal's Wager but has nothing to do with "what God wanted" or "God hating you"... It's more "if it doesn't work the outcome is the same anyway" (eternal oblivion in Pascal's case, certain death in this case), therefore why not give it a shot in case it does work.
Warning to anyone reading this: Pascal was NOT a self-help writer.
Somebody has to pay for the trial. Drugs are expensive and the amount needed to dose a single person is orders of magnitude more than mice. So who funds the study?
If it's the government or philanthropic fund, you have to put in a grant and show that it's competitive in terms of preliminary results etc.
If it's the drug companies, you have to deal with lots of complicated things with combination therapies. Drug companies don't like their drug paired with other drugs that aren't in their portfolio. They also need to see a way to make a profit on it, which means they need to evaluate whether this is the most likely successful trial, assess bang for buck etc.
If you want to go compassionate use, then you need to get the pharma to donate the drugs or insurance to cover it. This is spain, so I guess insurance is just the government since they have universal healthcare. I have no idea how that works but I am guessing it doesn't move fast.
> So who funds the study?
The End Users !!!! This is why medicine is too important to leave to drug companies, governments, or philanthropic funds.
What we need is an open source medical trial system with some bona fides
> what's the worst that can happen?
The patient dies from complications of the drug's use before the cancer.
If I had 6 months to live, and had no other options, I wouldn't care if a drug killed me in 10 days. Give me the option.
Fine, what if the drug causes a violent psychotic break and you harm your loved ones?
What if some weird interaction sensitizes your nerves, and you spend your last weeks in incredible pain, begging to die? Not only would that suck for you, it would, again, affect your loved ones. It would also cause distress to the nurses that cared for you and the doctor(s) that administered it to you; remember, they don't just have to convince you, they have to convince medical professionals that this wouldn't be violating their code of ethics.
>If I had 6 months to live, and had no other options, I wouldn't care if a drug killed me in 10 days. Give me the option.
you're not being creative enough.
I agree with compassionate use cases, but be creative here : some drugs can create deaths much more miserable than the controlled burn of a 6 month descent into hospice care surrounded by family and loved ones.
6 months to live versus a possible supportive drug regiment with the side effects being constant pain until you slowly bleed out through your eyes after total sensory lock-in -- easy a choice to make? not for me.
bigPharma doesn't care about that. They care about the publicity of their drug killing someone faster than the cancer.
No. No no no.
Big Pharma needs good data. And they have annoying FDAs/whatever-regulations-body slowing them down.
If you have a serious disease they might not mind you taking it. But if you have a serious disease plus your kidneys have already shutdown - w/e drug won’t save you. The death counts as a negative. “Let me take it anyway” well fine but it’s not some huge conspiracy.
It's not just those two choices though. It could be "6 months in relative comfort" and "10 days begging each minute to die but you can't because you're borderline unconscious". Or anything in between. Just saying.
Medical guidelines are there for a reason and are often, as they say in the military, "written in blood".
Having seen the last ten days of pancreatic cancer, there isn’t really a difference with what you’re describing.
Yes I (sadly) know. I commiserate with your loss.
> "10 days begging each minute to die but you can't because you're borderline unconscious"
They aren’t going to know if it does that until they give it to a human in the first place. The only difference in giving it now is they lack a control group.
Having seen a family member die absolutely horrifically in a matter of weeks due to late-diagnosed pancreatic cancer, I'd consider suicide if I got the same diagnosis.
Yes I (sadly) know. I commiserate with your loss.
Still wouldn't let my loved ones try untested treatments though, especially if it buys only weeks of extra lifetime. The potential costs are too high.
I found this green block in my back yard. It killed a dog because he was mostly cancer I think. Anyways just sign over hundreds of thousands of dollars, thanks! This will probably ki—er, cure you. What have you got to lose?
In a purely rational world who cares. 4 months is not all that far away from 6 months and with cancer you’d probably prefer to not be alive for those last two months anyway. We should be willing to do Hail Marys with 5-10% chances of success rather than doing absolutely nothing.
You would destroy any inheritance your family might get, or which could be donated to a cause saving a dozen lives, over a 5% chance you don’t die from cancer specifically, which might make you feel unbearably bad until you DO die? Like much worse than you already feel? That’s insanely irrational.
Edit: and all of this is before the psychological implications of knowing your time is almost up. People would rather have burnt skin removed by a painful grinder than painless maggots because bugs and being eaten are so psychologically scarring most people won’t even consider it until they experience the pain of the flesh grinder work. People won’t think rationally anyways until it’s much too late.
Sorry what’s the inheritance logic here? Are you talking about life insurance or something? Otherwise, and again presuming the cure doesn’t work which seems absent from your assessment as a possibility, how would it affect someone’s inheritance?
My general understanding is life insurance almost never actually pays out, and if it does it’s after a long fight and for less than you signed up for, and in any case should typically not be the largest portion of your inheritance.
That all aside, taking a risky but possible option that may mean survival, as a conscious and informed decision, even if aware it may void a possibility of a life insurance payout, doesn’t seem like a decision we have more right to make than the person affected by it.
Term life insurance really isn't expensive, and it's meant to take care of those you leave behind in an unfortunate event. Pay off some big bills so your partner isn't grieving AND homeless. Most of the people on this site are pretty well-off, and can/should afford an expense like this.
If you've got a 95% chance of death, take the pain pills and enjoy your final days. Don't bankrupt yourself and spend more time miserable, dying anyways.
Life insurance has a small 2-5% denial rate and most of those are lying big on the application. What are you talking about.
Knowing whether drugs work isn’t trivial. Patients are typically very heterogeneous in their responses to drugs. For example, pembrolizumab (the most successful cancer drug ever) typically only works in, say 30% of patients depending of the cancer type. Just throwing therapeutic ideas out there and letting physicians sort out how to use them and in which patients, isn’t a panacea. Looking at clinical data can be like star gazing even in planned studies. Structured, statistically powered studies, and costly rigorous assays on biomarkers and correlative studies are essential for understanding how and in what patients drugs are working. I’m all for expanding access to drugs, and there is abundant waste and greed in big Pharma and venture, but there are also people doing hard expensive science, medicine and manufacturing. Im not sure I have the answer. A “yelp for medicine” won’t improve immediate outcomes, nor longer term understanding and progress. A great and excruciating read about the tension there is a real-time blog (the story’s story) that was written by Jake Seliger unt he passed in 2023.
Things are, at least, getting better with the passage of right to try laws: https://en.wikipedia.org/wiki/Right-to-try_law
These drugs seem to all be only allowed after Phase 1 trials, so still not quite at the level you're describing here.
If nothing else, it's not the only hail mary you could potentially go out on. Would you give up the potential of being part of a trial for a drug that has actually done the work and demonstrated real promise in various pre-trial tests just to take a gamble on this alternative which hasn't even had the initial test replicated yet?
Further there is the potential for a false negative. If they don't understand enough about how the drug would work in humans, they may trial inappropriate doses or delivery methods. If those don't help or make things worse, it could be mistaken for the drug being ineffective and lead to the whole line of inquiry being abandoned. Then not only do you die, but countless others are potentially harmed by an effective version not being developed.
Finally, cancer treatments aren't just for the terminal. Drugs which primarily help during the early stages by necessity need to be trialed on people who still have a chance, maybe even a decent one, going with other, well established treatment options.
I had a relative who died from this around 20 years ago. 50yo slim, sportive and healthy and after going to a diagnostic as she didn't feel good, she was gone within a few months .. So yeah, if there is even a slight chance it works, this should be tried and that'd save people :(
We might take it too far, but the fear of quack medicine is extremely rational.
Every time I see homeopathic medicine on the shelves in a pharmacy, I think we’re not taking it far enough.
Every time I see homeopathic medicine on the shelves in a pharmacy, I think we’re going to need 100000x more
> Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths...
Our society leaves people to freeze to death in the streets.
Our society demands terminal cancer patients suffer the pain and social indignity.
It doesn't provide comprehensive single payer healthcare.
Our society is broken across contexts.
The ethics of life and death are murky at best. When is it acceptable? 6 months to live? 1 year to live? 5 years? What is the cut point? The answer is, there isn't a clear answer. Yes, that is a cop out, but it is also true. I agree with allowing people of sound mind to make informed healthcare decisions towards the end of their lives that involve high risk. but I would be wary of weakening the process too much. We should have a push-back because people in these positions are exceptionally vulnerable and therefore easy to take advantage of and, even worse, likely to be unable to defend against abuse for very long. Weakening this process would likely lead to drug companies doing what they always do, abuse their position for money. Why even go to expensive traditional trials? Just give some promising, cherry picked, results in a press release and now people are coming to you signing every waiver and paying their last penny to live next to the trial that will kill them because the drug wasn't even close to ready. I would likely feel very different if I was near death, but that is the point isn't it? Again, I'm not saying this shouldn't be an option. I just think it needs a lot of scrutiny and a high level of skepticism.
That’s because we have a system that financially punishes fraud and mismanagement which is what we want and should keep.
There should be a way for terminal cases to volunteer for early trials and I believe there is already legislation that provides that but it’s not used and funded enough.
good news, are current FDA has many ways of fast tracking a treatment and a willingness to do so
IMO, if you view your question from the ethical framework of "do no harm" i.e. the hippocratic oath instead of "move fast and break things", I can clearly see reason for the apprehension. The standards aren't positioned to catch "quack medicine" but to require full understanding before asking someone else to put something in their bodies. It's somewhat of an entitled stance that youd be okay with other people possibly needlessly dying in any circumstance for something experimental, and not one I'd ever want taken as an official stance by a regulated medical body.
Consider what the oath actually says.
> I will not give poison to anyone though asked to do so, nor will I suggest such a plan. Similarly I will not give a pessary to a woman to cause abortion. But in purity and in holiness I will guard my life and my art.
Now consider that doctors in Canada and Europe are literally administering MAID as we speak. In other words, administering poison with intent to kill. Further, consider that doctors have participated in administering lethal injections, etc. I could go on all day.
But you'd invoke the Hippocratic Oath to deny people with fatal diseases access to potentially curative treatments, though admittedly experimental? That's a funny view of the oath you've got there, and either an uninformed or very funny take on medical ethics, as well.
That's not an oath that many modern doctors will have sworn though -
(From wikipedia) As of 2018, all US medical school graduates made some form of public oath but none used the original Hippocratic Oath.
I imagine the story is similar elsewhere.
> Our society's morbid, irrational fear of quack medicine
It is not an irrational fear.
Brandolini's Law applies: "The amount of energy needed to refute bullshit is an order of magnitude bigger than that needed to produce it."
The only way to prevent quackery is to cut it off hard before it gets started.
Wakefield demonstrated the disaster that happens when you don't.
(And if you have been reading this site for very long, you know the experimental treatments are already around--we're not currently lacking for possible cancer treatments. The problem is finding the trial. Then the problem is getting people through the process and then getting them to the trial. See: "Please be dying, but not too quickly": https://bessstillman.substack.com/p/please-be-dying-but-not-...)
Even if I grant that argument, what I've described isn't even quackery. It is legitimate medical research and experimentation, and what doctors in olden times would call a "heroic" intervention -- but, sadly, now this sort of thing has become collateral damage in the war between medicine and quackery. And patients are the ones who die and suffer because of it.
The general public, as a group, cannot identify quackery. People died from bleach and horse dewormer to prove this. The continuing career of Mehmet Oz also demonstrates this.
There will always be more malevolent actors looking to take advantage of people than there are benevolent actors able to protect them. Standard rules and laws are an attempt to at least protect the majority of the people the majority of the time. Like anything, rules are never perfect, and you have to weigh the limitations against with the benefits.
As someone who has literally trawled the cancer trial databases for people, lack of trials is not the main problem--finding the appropriate trials, on the other hand, is terribly difficult.
If you really want to help people, apply AI to help common people search all the public cancer trial filings to connect up the patients and the doctors. That would do far more good, far faster than changing laws and rules around last ditch experimental treatments. You won't become rich, but you'll help medical science a lot, and you might even save a life here or there.
Ethics is a topic I would never trust HN on.
Am I misunderstanding the headline? Is the word "block" now meaning "enhance" instead of "stop"? I would think based on the text of the article that it enhances resistance. Or are tumors necessary to stop cancer growth (even though it is cancer growth?)
> Am I misunderstanding the headline?
Yes, what’s being blocked is “tumor resistance” to treatment.
“potentially overcoming treatment resistance in one of the deadliest cancers.”
It's an awkward headline that, when read a certain way, says the opposite of what it means.
if that holds true in humans that would be a huge win. but it would be interesting at which stage those drugs still help. btw, it is said Chris Rea was diagnosed with pancreatic cancer at the age of 33, he died last year at he age of 74. it would be interesting to know what circumstance helped him to fight the cancer for such a long time
> These agents together were tested in orthotopic mouse models of PDAC, where tumour cells are implanted in a location that closely resembles their natural environment in the pancreas.
Ugh, of course: "in mice"!
> The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).
OK, maybe "in human tissue grown in mice" isn't so bad.
Fingers crossed. Pancreatic cancer is terrible.
I was wondering what preclinical models meant. It would be more accurate to call it animal models. I read roughly 3% - 5% of compounds move from preclinical cancer therapies to fda approval. That’s a tough success rate.
Anybody read that as "Dugtrio found to block tumour resistance..."?
"Here we describe peptides secreted as part of the Diglett evolution process, that have been found to disrupt oncocyte metabolism in vitro..."
As we are always starting with mice, I am wondering if there are some drug that could work on humans but not on mice.
Absolutely there is, which is why they haven’t genetically modify the mice for useful experiments.
It's funny how many years of "X found to be effective in fighting cancer" stories have filtered through HN and then you never hear about it again.
The research at treating mouse cancer has been making great strides--people cancer still has a long way to go though.
I have absolutely no idea what the current frontline treatment drugs are for literally any form of cancer, and would bet the same is true for almost everyone else here. Most of the exceptions are people who know the frontline treatment drugs for one or two forms of cancer that impacted them personally. "And then you never hear about it again" is subtly implying that the drugs behind headlines never proceed beyond that point, but I didn't hear about it when the current frontline became the frontline treatment for any form of cancer. Most people just aren't in the loop about the evolution of the field of oncology, beyond pop-sci headlines.
And yes, most headlines like this don't result in changes to the care provided to anybody outside of clinical trials, but some do, and you and I probably won't hear about those either.
People cancer outcomes have improved a lot in recent decades. Many forms of cancer are essentially cured if you detect them early enough.
What's the best protocol for detecting them early enough, as an annual set of tests that a non-crazy / non-rich person would go do?
The stories are written for a general audience and often lack detail or nuance. "Promising" doesn't mean "likely". "Possible breakthrough" is not a breakthrough. And it may just mean we learn something that we don't know today.
I lost my wife to metastatic melanoma a few years ago. Words used in reference to cancer are often terms of art that have a distinct meaning from the general meaning. Her particular cancer was pretty awful and lacked mutations that allowed for the use of targeted therapy that buy time. Even still, her chances of survival were about 65% in 2023 as compared to 0% in 2013. Unfortunately, the odds didn't end in her favor, despite the incredible efforts of a team of doctors at a national cancer center.
Anything with cancer research and treatment is an testament to standing on the shoulders of those who came before. Many people suffered to give my Molly those odds - she had hope where many others had nothing. And today, we have trials of custom vaccines that will offer others more hope and perhaps safer treatment. Perhaps in some small way her journey and ideal helped those or other developments. That's all we have.
As a rule of thumb, if you’re not a researcher in the area ignore any media reports of a study that include the words “in mice”.
Also, there’s a tendency on HN for commenters (mostly software engineers) to think that they are smarter than the scientists who work on this stuff day in, day out. Let me tell you, you, random HN reader are not smarter than random biomedical scientists.
I think this is one of the expected outcomes of "Science by Press Release" (universities motivated to maximize their grants and IP), combined with media/press that wants clicks (articles that talk about cures for cancer get clicks).
It's not funny how people make judgments like this without any factchecking, just by their gut.
Talk to any actual healthcare worker from an oncology ward. (A nurse will do.) With most cancers, your chances of survival are non-trivially better now than even in 2010. Immunotherapy absolutely exploded in the meantime. For example, the vast majority of monoclonal antibodies (not just for treatment of cancer) were only approved in the last 15 years.
There are some notable holdouts like glioblastoma and pancreatic cancer, and these tend to draw attention. But there is real progress.
At usual baity headline. It's in rat, it's on a tumor model, so there is a good chance it's like the other thousands mice studies that do not replicate on humans
At this point, hasn't every permutation of cancer drug cocktail been tested on mice?
This should be seen as a warning of how much time and efforts and money and stability are required to cultivate a discovery that could have never happened.
Spanish researcher from Madrid. Hired by US on a grant. Worked hard and became director of the Oncology department on the NCI on Maryland. Somebody on the Spanish government decided to bet strong on him and recover it for Spanish Cancer research. A specific customised job offer was created for him. Politicians came and go; some are sensitive about science, other not so much. Some promises were never fulfilled, and he was about to quit and migrate again until private companies stepped on the scene with the resources needed and the will to allocate those resources. Money well spent, that was about to never find his target.
Nobel prizes were created exactly for this kind of humble, serious, zero-nonsense, zero-drama, all-work scientists.
The question here is: how much "Barbacids" quit US in the last year? Scientists aren't stupid. Everybody is aware that Barbacid in US today would have being harassed just for speaking Spanish and having a scarred face. All points that US is bleeding talent at a level never seen in their history.
I wonder what it would take to get people to stop up-voting animal model cancer cures?
Guys, these are a dime a dozen and you never hear about them again.
All like 6 stories from this site on hn are some cancer cure that went nowhere.
IN MICE. (To be fair, also IN SOME OTHER BETTER MICE).
https://jamesheathers.medium.com/in-mice-explained-77b61b598...
(mostly a joke, but I'd be in favor of adding context to the HN headline if possible)
This context is very important.
"Little by little, over-inflated results and breathless breakthroughs betray trust. They throwing dimes in a wishing well which people rapidly start to expect will never pay compound interest."
"Then, when one of those people is elected to parliament, or Congress, and start to cut the budget for the National Science Foundation, or declares that All Research Should Be In The National Interest (whatever that is), I wonder how much we reap what we have sown."
This isn't quite as bad as the garden variety "in mice" studies:
> The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).
PDX is a double edged sword. Human tumors are engrafted into mice with no immune system. Immune-cancer interface is incredibly important, yet completely lacking in these models. Consider that some of the greatest cancer drugs ever work specifically on the immune system (e.g. checkpoint inhibitors like Keytruda).
A drug that works even without help from the immune system seems like it might be even better. It's hard to imagine how the immune system might interfere, since it doesn't interfere with other drugs.
>"The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice"
Required XKCD: https://xkcd.com/1217/
Is PDX considered to be illegitimate? Would be curious to know if prior studies that showed success with PDX methods ultimately resulted in useful therapeutics.
Vorinostat
I wonder how long until we'll start seeing these breakthrough cancer treatment articles for clinical trials done in dogs. Oncologists think dog research is a better fit than mice because of greater genetic similarities to humans and the fact that pet dogs live in similar environments as their owners. I think in general people definitely wouldn't be as ok with inducing cancer in dogs as in mice, but finding volunteers owners of dogs with existing cancer is certainly easier.
That's interesting because rodents and apes share a more recent common ancestor (75Mya) than dogs and apes (85 Mya).
I used to work at a biomedical institution that did cancer treatment experiments on dogs. There was basically a kennel and periodically they would take a dog and irradiate it.
That was fine in the abstract, but there were computational labs above the kennel and periodically you'd just get this huge outporing of dogs barking and howling and it was really hard to get any work done.
Mice have the best drugs.
Also the worst. You win some, you lose some.
I opened the comments fully expecting the top reply to be “In mice.” Bingo.
There really has never been a better time to be a critically-ill mouse. They've got something for you.
I've been playing to much pokemon with my kids, read this as "Dugtrio"
there must be some sort of word for "games-bleeding-into-real-life" for stuff like this.
I remember years ago playing some games, and hearing similar sounds in real life would startle (or amuse) me. And you can't really explain it to anyone around you, lol.
tetris effect! https://en.wikipedia.org/wiki/Tetris_effect
There's an elevator in a building where I attend meetups. A staffer has to authenticate with a card in order to let you use the elevator. Once it authenticates, a chime plays that goes sol-do-mi-sol. These four notes also begin the main bit of the Super Mario Bros. 2 overworld theme which I find myself humming.
It's okay, I thought it was a drug cartel
Same, I'll never look at them the same again.
thank you, I did a double take. Drugtrio is my new favorite Pokémon
me too
I read this as "Dugtrio found to block tumour resistance".
As in the Pokemon.
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> The results demonstrated the therapy not only reduced tumour size but also entirely stopped tumour growth with no evidence of tumour resistance for more than 200 days after treatment.
More details in https://www.pnas.org/doi/suppl/10.1073/pnas.2523039122/suppl... See page 25
In mice, N=12.
1 survived 200 days without cancer and was euthanized for 'ocular ulcers'.
5 survived 50-150 days, without cancer but were euthanized for other health problems
6 survived 50-150 days, and still had a smaller tumor and were euthanized for other health problems
My take away: Interesting, but the press article is overselling the result by a lot.
Edit: Fixed link.
So: half (1+5) of them made it at least 50 days without cancer, and the other half made it at least 50 days with a smaller tumor? This sounds excellent to me. I agree that the sentence you quoted is overselling, though.
Apparently 50 mice days is equivalent to about 5 human years, so even if these other causes of death here directly caused by the treatment (not alleged), surviving this much longer (5-20 years) would be pretty incredible for humans.
Where did you get that "50 mice days is equivalent to about 5 human years"?
Mice are short lived, so the time for some events like sexual maturation are shorter.
On the other hand, the problem with cancer is that it adapts, it "learn" how to avoid the effect of the drugs, or how to make the signals to get more blood vessels, or ... I think most of these only depend on how many times the cancer cells reproduce to get a lucky adaptation, so for these effects 200 days is only 200 days.
Also survival rate depends on how early it's detected. In a recent post about colon cancer, the mice got the treatment like 2 weeks after the cancer cells were injected. My guess is that this study also has a short time before the treatment.
Early detection improves survival rate a lot: https://www.cancerresearchuk.org/about-cancer/pancreatic-can...
> Localised: More than 25 out of 100 people (more than 25%) survive their cancer for 3 years or more after diagnosis.
> Regional: Around 15 out of 100 people (around 15%) survive their cancer for 3 years or more after diagnosis.
> Distant: Only 1 out of 100 people (1%) survive their cancer for 3 years or more after diagnosis.*
Also (combining all detection stages):
> Generally for adults with pancreatic cancer in the UK:
> around 5 out of every 100 (around 5%) survive their cancer for 10 years or more
Mice are very short-lived compared to us. In humans, the usual standard of judgment when it comes to cancer is "5 year survival". No mouse has ever lived for 5 years yet, that would be like 180 years for us.
Prolonging a mouse's life by a few months is non-trivial and hints (only hints) at potential efficiency of such treatment in other species as well.