May peace be unto him, you, and the rest of your family.
When (if?) you feel ready, there is an organization [1] whose mission is to support siblings, parents, and grandparents of children who have died at any age. I have been heavily active with them since losing my only child 9+ years ago. I commend them to your attention. (Once again, when you feel ready.)
Hope this makes it to people soon. Have a family friend who was diagnosed with cancer a few days ago. It was here in Canada, so they offered her assisted suicide, literally within 30 seconds after telling her she had cancer. She didn't even really process the diagnosis before they were offering to help her die. They didn't offer to try any experimental medicine.
Not a comment on the parent post's situation, but MAID in Canada isn't quite turning out how it was promised. A recent report making a splash in certain circles pointed out that ~200 people in Ontario in 2023 got assisted suicide either the same day or the day after they filed their paperwork. The most notable case was a woman who, after submitting her paperwork, changed her mind and wanted hospice instead. However, she was denied hospice care and subsequently was put down.
Bit by bit, Canada risks defaulting to suicide over expensive care. That's not what people voted for when it was first proposed.
The problem isn't that the urgent request went through, it's that she requested hospice or palliative care and was denied. And, let's be honest, POA should not be sufficient to euthanize a person who is awake, aware, and revoked consent.
"Do no harm" has been replaced with "put them down if it's cheaper and we can get away with it"
That's a separate problem from the parent post, and the point of my post was that her husband requested the decision on the assisted death, not the government.
I didn't mean to suggest that the government is going to hide under people's beds and stab them in their sleep if they get sick.
The government is responsible for funding every aspect of this process, though. It regulates the controls and rubrics over who gets what kind of care. The husband may have instigated it, but the system is broken if a person eligible for euthanasia isn't eligible for palliative care or hospice.
Most importantly, I continue to contend that MAID is turning into something that isn't what Canadians voted for. It is, however, turning into something that its opponents feared might come to pass.
Thats how I read it as well. The deeper issue is that he shouldn’t even be able to contact them when they deemed her lucid enough to not be eligible just a day earlier, especially when they were keen enough to notice he was burned out.
Separately, why do these services have to move so quickly? It seems like it’s either glacially slow in other countries where people pass before even finishing the paperwork, or insanely fast like in this case. There really should be a balance.
Since we're talking about Canada, ostensibly the government, as the provider of healthcare, wants it to be inexpensive enough that the citizens have a first-world level of care... as opposed to euthanizing sick people because it's easier than providing hospice or expensive treatment.
After all, using the monopoly power of government and taxation is meant to be more efficient and provide more services at lower costs.
A cynical person might presume that MAID is being used as a cost savings measure more than an empathetic alternative for those who do not wish to wait to die of natural causes.
Are the headlines the tip of the iceberg, or the exceptions that gain notoriety? When the government and health care system are so deeply intertwined, who has access to the data but not an incentive to obscure the facts? With any luck, time will tell.
Oh, mostly just the hospitals, the insurers, the medical device manufacturers, the pharmacy benefits managers, the pharmaceutical companies, the group purchasing organizations, and the clearinghouses. Everyone who can take a bigger cut if there’s more money sloshing around the industry.
That sounds like murder to me. I couldn't believe that and thought you must have been misrepresenting the facts. Nope, your summary is correct; the full case is there, in black and white, on page 22 of the Ontario Solicitor General's report, as you linked; and amazingly it was reviewed by a committee that didn't seem to find much wrong with it. That is very deeply disturbing. I have quoted the case overview below:
>CASE 4B
Case Overview
Mrs. B was a female in her 80s who had a challenging medical trajectory following
coronary artery bypass graft (CABG) surgery. She experienced several post-operative
sequelae, including wound dehiscence, osteomyelitis, and respiratory failure. She
required specialized care in hospital, including additional surgical procedures. Due to
physical and functional decline, Mrs. B elected for a palliative approach to care. She
was discharged home with palliative supports (i.e., palliative care team and home care
support services, including adaptive aids and personal support services).
Mrs. B reportedly expressed her desire for MAiD to her family. In response, and on the
same day, her spouse contacted a referral service on her behalf. The following day, a
MAiD practitioner assessed her for MAiD eligibility. She reportedly told the MAiD
assessor that she wanted to withdraw her request, citing personal and religious values
and beliefs. She communicated that pursuing in-patient palliative care/hospice care and
palliative sedation was more in-keeping with her end-of-life goals.
The next morning, Mrs. B presented to the emergency department (ED) of her local
hospital. Her spouse was noted to be experiencing caregiver burnout. Mrs. B was
assessed to be in stable condition, and thereby discharged home with continued
palliative care. Her palliative care physician completed a referral for in-patient palliative
care / hospice care due to her social circumstances (i.e., caregiver burnout). Her
request was denied for not meeting hospice criteria for end-of-life, and a long-term care
application was offered.
On the same day, Mrs. B’s spouse contacted the provincial MAiD coordination service
requesting an urgent assessment. A different MAiD assessor from the previous day
completed a primary assessment and determined Mrs. B to be eligible for MAiD. The
former MAiD practitioner was contacted. This MAiD practitioner expressed concerns
regarding the necessity for ‘urgency’ and shared belief for the need for more
comprehensive evaluation, the seemingly drastic change in perspective of end-of-life
goals, and the possibility of coercion or undue influence (i.e., due to caregiver burnout).
The initial MAiD practitioner requested an opportunity to visit with Mrs. B the following
day to re-assess; however, this opportunity was declined by the MAiD provider due to
their clinical opinion that the clinical circumstances necessitated an urgent provision. An
additional MAiD practitioner was arranged by the MAiD coordination service to complete
a virtual assessment. Mrs. B was found eligible for MAiD by this third assessor. The
provision of MAiD was completed later that evening.
Experiencing cancer in my family I can tell for sure all of that buzz is quite exciting, but in the last 5 years there haven't been breakthroughs that would significantly improve outcomes for an average patient.
There have been massive improvements in treatments in the last 5 years. Sure, cancer is far from being "cured" - but survival today is far better than 5 years ago for many forms.
Among many others:
- CAR T therapy going from lab to oncology suite (first launch 2017, but use rapidly growing)
- Liquid biopsy going from lab to PCP's office - starting with Grail Galleri and moving from there (yes, the NIH results were weak, but the idea of a liquid biopsy at all would be laughed off 10 years ago)
- Move of Atezolizumab and Tecentriq from infusion (hour) to injection (minutes) to increase availability
- Lower dose CT scanning for lung cancer, including for non-smokers
And a long line of immunotherapies that are making the leap from lab to chair right now.
The last 5 years have probably been the most exciting in cancer research since the launch of the monoclonal antibodies in the early 2010s. There is still incredibly far to go, but the trend is in the right direction: https://employercoverage.substack.com/p/decline-in-cancer-mo...
Long answer, it's a variable you need to consider when doing data analysis, and it depends on what exactly you're talking about, but it's absolutely not true for improvements in cancer survival general. One alternative method is to look at per-capita death rates, for example:
Reduction in global age-standardized cancer death rate since 2000
(Scroll down to second graph. Since the population is getting older, age-standardization makes a fairer comparison)
https://ourworldindata.org/grapher/cancer-death-rates
2000 is an arbitrary year I picked for clear visual changes without needing to haggle over statistics. If you want to feel optimistic, switch the childhood cancer death graph to 1960-now.
This method has different possible failure points. It could be that less people are getting cancer, or that people who would get cancer are dying of other causes, or reporting of cause of death has changed, though this is very unlikely for some figures, such as leukemia death rates for children in the US. Statistics is hard. Overall though, the evidence is very good that cancer survival has improved a lot due to better treatments since 2000.
If you have a more specific claim you're dubious about, I'd be willing to look into it for you. I'm very enthusiastic about this topic.
Combined with your data, that implies that whatever wins we got from decreased cancer rates (e.g., less smoking) or improved treatment have been squandered elsewhere (probably obesity / heart disease).
If life expectancy had dropped over that time, then I guess it could be that cancer was as deadly as ever.
I wonder what the deal is with Greenland in your dataset. Lots of smoking? Lots of radiation?
I'm not exactly dubious about anything really, it was just something plausible I had heard a while ago and, while I don't recall where I heard it, I must have given it some credence for it to stick with me.
IIRC survival improvement has happened across all staging categories, including the worst one (IV, distant metastases found), so the answer would be "no".
A friend of mine, aged 50, has worked in pediatric oncology her entire (nursing) career. The ratio of surviving kids has flipped from 30/70 to 70/30 during her tenure.
Cool question. What form would an answer take? We need some detection benchmark data thats invariant over the period of interest. I hope the data exists but I would be surprised.
Another way to come at it would be mortality data. But that has a bunch of its own problems.
Everything is changing at once, it makes this kind of science so hard.
mRNA cancer vaccines are the most exciting new treatment about to hit the clinic. Moderna's Phase 2b intismeran autogene randomized trial found a 49% (!!!) reduction in the risk recurrence or death for patients with high risk melanoma already on standard treatment. Several Phase 3 trials are underway. mRNA vaccines have the potential to work for a wide variety of tumors.
(95% confidence interval is 0.294-0.887, wide but not too wide, n=157, to be expected for phase 2).
How they work is also completely fucking insane. Intismeran autogene is personalized for every patient via sequencing their tumor DNA. That's sci-fi shit. If you're not impressed by that, you should be. Fast and scalable DNA sequencing, neoantigen identification, RNA synthesis, none of this is easy and all of it relies on recent innovations across multiple fields.
The first proofs of concept for personalized vaccines like this date back to 2017[1] or 2015[2]. The process for designing the vaccines requires a machine learning algorithm first published in 2020[3]. Details of the algorithm aren't available, but it validated against data published in 2019[4], and there have been many recent advancements in algorithms and datasets for biotech ML that it likely relied on. As you might already know, mRNA vaccines were first tested in humans around the 2010s[5].
It may feel that way due to the iterative nature of medical improvements, but over the past few decades there has been a consistent reduction in cancer mortality rates across most types of cancer [0]. Treatments really are getting better and more targeted. Immunotherapy has made huge breakthroughs. Combination treatments allow for significantly improved lifespans and better quality of life during treatments. There are a few cancers that remain hard to treat, but I have a lot of confidence that in the coming decades we will make strides in attacking them. That being said, I'm very sorry to hear about the pain you and your family must be going through. I've had a few close loved ones undergo cancer treatment and it was tough.
Examples aside, 5 years isn't long enough for a treatment to move from early mice trials to clinical use. The average time from application to FDA approval is about 10 years.
The breakthroughs happening now will benefit average patients later. It's frustrating, but it's not because we've run out of innovations.
Major breakthroughs of the kind you’re talking about are extremely uncommon. Instead it’s lots of little gains that keep adding up because cancer isn’t adapting overall people still get the same mutations they got 10,000 years ago.
So average person with cancer does better when any individuals cancer treatment improves and it keeps compounding over time. This doesn’t mean everyone with cancer gets a slight improvement, often it’s specific types or stages that improve without impacting others. Where general progress comes from is it’s not the same improvements year after year.
https://en.wikipedia.org/wiki/Timeline_of_cancer_treatment_d...
I won't debate what merits a major breakthrough. I will say, that while there hasn't been any major developments in the past five years, I can't draw any conclusions from that tidbit of information.
That cuts out in 2015, but 5 year survival rates keep increasing with the USA just crossing 70%. Though across longer timeframes some of that is from early detection; even limited to late stage diagnosis the statistics still show significant improvement. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac...
(Having not read the article), most likely because the cancer cells (at least at more advanced stages) are busy trying to replicate as fast as possible, so they take up nutrients at a much faster rate than non-cancerous cells. As to why Iron in particular, it is used as a cofactor for enzyme and if Iron is a limiting factor for replication then supplying it will lead to a burst of growth which then (presumably by applying strong oscillatory magnetic fields) you can target those cells directly to locally boil them.
How do the iron nano materials get there? probably a combination of vasculature and diffusion.
They have done this kind of stuff before with gold nanoparticles, iron is a lot more abundant.
I agree, or at least I would stress that people should be allowed to consent to that.
I don't know what the prevailing medical ethics of doing that kind of thing in consenting patients
in that state, but my uninformed intuition is I would disagree with it.
Though one thing that I might think researchers might not want is people may be too sick to recover even if their cancer disappeared tomorrow.
Both patient participation in clinical trials and compassionate use of experimental treatments are fairly common for cancer patients, with various accessibility barriers. (One issue with the latter, for example, is that the incentives aren't lined up for companies to provide unapproved drugs to dying patients, you're way more likely to get a horrible complication that leads to bad press than a miraculous recovery).
It's around 10-15% for the whole drug I-III flow (13.8% according to [1]), but that varies dramatically based on therapeutic area. On the order of a third of infectious disease vaccines might be approved but only maybe 5% of oncology therapies because the latter often have a different standard for approval so it's cheaper to run trials.
That's interesting, but I was talking about the success rate of someone with a terminal illness going the clinical trial route. Sorry, I now see that my question was not so precise.
For cancer, it doesn't seem to impact survival odds at all [1]. In other fields it may improve metrics a small bit but that's largely because in clinical trial patient selection, they're very careful to exclude anyone with an even remotely confounding factor (like weight/BMI).
This is why people begging to take untested, unknown drugs in the extreme off-chance of they work is generally a bad approach. It almost never works, and it encourages the earlier release of ineffective drugs to a wider audience.
If someone is about to die and you save them at the last moment, aren't you basically reviving a zombie at that point? He has eight new tumors. You can pop almost all of them and still be left with a terminal patient.
Even if you're buying time with every trial, all you've done is turn the patient into a lab rat for physicians to play around with. The ideal patient needs to be dead enough to have no human rights, but alive enough to participate in the trial. The hope of a miracle cure means the patient doesn't believe himself to be dead enough to not have human rights anymore. It's a paradox.
Signing the documents for such a trial is equivalent to signing your consent for euthanasia. It shifts the blame of death from the cancer to the company performing the trial. It's an extended form of organ donations where you donate your entire body while you're still alive.
In the US, the FDA has a Compassionate Use exemption to clinical trials for exactly this circumstance!
There must be informed consent, no reasonable alternatives (which, in cases we deem terminal, is often the case), and some evidence pointing to the treatment possibly being helpful. It's an excellent ethical program that gives patients a choice and advances science.
In my experience most legitimate biotech companies working on promising drugs and therapies don’t want to touch the exemption with a 30 foot pole. Since they raise most of their money from the public to fund clinical trials, a single bad reaction could generate enough bad PR to derail fundraising and kill the drug. Sticking to clinical trials allows them to control that blast radius so even though the FDA approves >95% of applications, in practice very few drugs are available that way.
The biggest exception is oncology. Since everyone knows that chemotherapy is hell, cancer drugs tend to get a pass and pre-approval companies are (slightly) more willing to work with compassionate use exemptions.
Both of my parents have benefited from access to early medical trials. One is currently very late stage IV cancer. Access to trials is usually proxied through respected doctors/oncologists affiliated with major hospitals rather than offered broadly. I assume for reasons of experimental protocol and integrity the overseeing doctors are typically not the same as the conceiving research team.
That is exactly how clinical research works. My mother worked running clinical trials for two decades.
When she was diagnosed with leukemia she was able to get into a research study herself that gave us 10 more years together.
One of the horrible but necessary parts of trials is the control group, who receives placebo. This is only done in a few of the trial phases but is essential in measuring efficacy. If someone wants to throw their brainpower and a little bit of AI/tech at the problem, you could end up eliminating a lot of suffering.
AI and tech won't help, but if the threshold to try a drug were adjusted to exactly the right threshold, where enrolling in a study would be expected-value neutral (this is by marginal reasoning), taking a placebo would not be worse than not.
I'd think AI and tech could solve the problem pretty easily, assuming the study authors could get access to the health records of everyone that was not in the study (and could therefore generate control cohorts by looking at large samples of comparable patients outside the experimental group).
This is done for targeted advertising all the time. Frustratingly, the surveillance capitalism industry is precisely the reason the dataset you'd need probably shouldn't exist.
Maybe we'll get some decent lawmakers sometime soon, and problems like that will be fixed via legislation. They'd need to ban the root-cause of the problem. I'm guessing it's more likely the current congress will let private companies steal + sell everyone's info instead.
"When we systemically administered our nanoagent in mice bearing human breast cancer cells, it efficiently accumulated in tumors, robustly generated reactive oxygen species and completely eradicated the cancer without adverse effects ..."
So it kills human cancer and doesn't harm the mouse in the process.
Xenografted human tumors in mice != human cancer. The support structure of the tumor (tumor microenvironment) differs between model mice and humans, cells derived from human cancer that can be cultivated in a lab and xenografted differ from typical human cancer cells, and xenografting requires immunodeficient mice, just to name a few factors that affect treatment response.
Mice models of cancer are useful, but you should never be too surprised when something that works in mice doesn't work in the clinic, xenografting or no. Cancer is complicated.
Actually, when in the lifecycle of developing a treatment does anyone have a real idea of what cost will be? Can anyone know this yet?
In terms of where _prices_ are set, that negotiation is a function of efficacy relative to other things in the market right? If it ends up treating cancers that each already have a reasonably effective treatment, maybe the pricing isn't that high -- but if it is effective in cases where currently there are no options, the price should be high?
But for something that potentially works against a range of cancers, should we expect to see a sequence of more specific trials (i.e. one phase 1 for basic safety, a bunch of phase 2s for efficacy on specific cancer types, a sequence of phase 3s in descending order of estimated market value? And in 10 years, Alice and Bob with different cancers will pay radically different amounts for almost exactly the same treatment but with small variations in some aspect of the formulation so they can be treated as distinct products?
Pharmaceutical companies don't just fund research without having a model of the expected costs to bring something to market, the expected market size, and the viability and cost effectiveness of other potential treatments.
They have entire teams of people who figure out the viability and pricing of therapeutics before the first dollar is spent, with estimates getting refined the further you get along in the cycle.
Does the cost matter? Many countries subsidize healthcare, so there's either no charge or a token payment which doesn't even pretend to cover the cost of treatment.
Other countries use insurance, so once again the end cost is essentially irrelevant.
The cost absolutely matters. If something costs tens of thousands of € per month for a long time then it will either not be approved or will be used very rarely. The cost is not irrelevant because the insurance does not have infinite money. They need to decide which cures, medicines, operations they fund. They can spend 1000€ to cure 100 people of something or to spend 100k to maybe cure someone with an experimental treatment.
This is one of the issues with the modern cancer cures, thst they are very specific to the cancer, the patient, need one off lab work for each patient and this makes them very expensive and not affordable to many. Despite having public healthcare the managers of it still need to decide what to spend their limited funds on.
The treatment cost for the newest hep C drugs have dropped dramatically since they were introduced. Started around $100,000 for a course. So six-figure price tags don't keep "cure"-level drugs from getting approved or introduced. The cost of the existing not-a-cure treatments also added up fast, after all; as they do for many cancers.
You're right about the specificity - Hep C is a bigger-population target than a lot of cancers are - but a lot of the new approaches are looking to be inherently more "personalized" to compensate.
> Other countries use insurance, so once again the end cost is essentially irrelevant.
I think it matters because oftentimes insurance companies won't cover treatments if a cheaper form of treatment exists. It doesn't matter if the old treatment is less effective or a much worse outcome for a patient. This is especially true for "new" treatments.
Cost is always relevant, given that the amount of money in any healthcare system is limited and someone must decide whether to pay for patient A or patient B.
No, they aren't: the second is irrelevant and unphysical. Highly-pressurised cores? Really? "Dense", I could buy, but:
• If there's blood supply, then (A) it can't be a much higher pressure than the blood pressure (unless there's some Rube Goldberg machine involving active transport), and (B) the tumour is reachable by treatments like this;
• And if there isn't blood supply, then the tumour's core is necrotic, and a treatment to kill the dead cells wouldn't do anything anyway. (Sure, killing the tissue that isolates a lump of necrotic flesh from the rest of the body might cause new and exciting problems, but somehow I think those might be preferable to incurable breast cancer.)
The second is just not a relevant criticism. The third, if it's an actual issue, can probably be worked around by tweaking the molecule slightly – and if not, suppressing the immune system isn't that difficult (it's a known side-effect of many chemotherapies). The first, if it's an issue, can be avoided by injecting the medicine near the target site.
I agree that this treatment might not work in humans, but all the AI's done is taken a generic list of potential concerns, and inserted technobabble to try to make it match the scenario. If you want generic criticism, see https://news.ycombinator.com/item?id=47209076: at least that's true.
You're incredibly wrong. You also cited my own comment at me.
The problem of high interstitial pressure (not blood pressure) interfering with drug delivery in tumors is basic cancer biology. If you don't believe me, here's:
A review published in a reputable oncology journal, with over 100 citations, entirely about targeting interstitial pressure, with an abstract leading with "Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment."
https://aacrjournals.org/cancerres/article/74/10/2655/592612...
Another review, also a reputable oncology journal, 1000 citations, about tumor stroma more generally, which lists high interstitial pressure as a mechanism by which tumors limit drug access and includes a nice diagram (Figure 2a).
https://www.nature.com/articles/s41571-018-0007-1
That's how basic this fact is. 1000 citation reviews in Nature have beautiful fucking diagrams of it. I'm pretty sure it was in the textbook of my undergraduate biology class.
If you don't know shit, don't talk shit. People will criticize LLMs for being overconfident while writing essays from their ass.
I did briefly consider that this was referring to intercellular fluid, but "highly pressurized cores" is a terrible way to describe high IFP, so I rejected that interpretation. I thought the LLM was "trying to" refer to some kind of dense-walled cyst. (Of course, the LLM wasn't actually trying to say anything at all.) (And I think my argument there about osmotic pressure, oxygen diffusion and tissue necrosis is correct: hypoxia's already an issue for tumours, and there are only so many heroic workarounds available before a cell's only option is to die; and since blood pressure is higher than even the high IFP found in tumours, that's the appropriate bound for the argument I made.)
Your interpretation leaves the LLM's discussion of stroma as a non-sequitur, since that is not why high IFP causes problems for drug uptake; and at that point, I think you're just substituting a correct statement in place of the LLM's superficially-meaningful nonsense. I'll go through it again, this time focusing on the names assigned to each point:
"1. The Scale of the Human Body" talks about the excretory system. The part of the explanation comparing "tiny" to "vast" is at the very least misleading, but I would call it outright wrong. And yes: I am also thinking of all those "well actually, the geometry of the circulatory system" interpretations that make it technically correct, but… if a biology teacher explained it like this, would you really think they were teaching it properly? (I mean, seriously, calling "The human liver, spleen, and kidneys" "the reticuloendothelial system"‽)
"2. Tumor Architecture", under your charitable interpretation, isn't talking about "architecture" at all.
"3. Immune System Differences" is at least named right; but a treatment that only works in immunosuppressed patients is still a treatment. You could imagine a cancer drug sufficiently-effective that it is worth suppressing the immune system just so you can administer it. (I don't think it's likely that this is one, but that's for experiment to decide. And if the patient's immunocompromised anyway…)
> You also cited my own comment at me.
Oops. That does make me feel foolish. In my defence: it didn't occur to me that anyone could think you were saying the same things as the LLM, because what you were saying was correct, and what the LLM was saying was nonsense.
Although, if you thought you were saying the same thing… is the LLM's "tumor architecture" supposed to refer to the tumour microenvironment‽ That would explain the stroma mention, but… wow that is not a sensible way to say that. I continue to assert that the LLM's badly-plagiarising some papers, lecture notes and/or textbooks, blended with bad pop-sci analogies to the point of incoherence.
Funnily enough, now that I've gone back and reread the LLM's explanations, I've decided that point 1, the one you were least critical of, is garbage whereas points 2 and 3 are fine.
1. Mice usually clear drugs faster, not slower, than humans, so either point 1 is wrong or I'm missing something, and either way it's a bad explanation.
2. This point is fine. The use of the phrase "tumor architecture" in this context is common, for example this random paper https://www.cell.com/cancer-cell/fulltext/S1535-6108(12)0008... and several papers cited by the Nature review. I don't get your problem with the phrase "highly pressurized cores" is, or what you're calling a non-sequitur.
Maybe you're arguing that it's an oversimplification to imply that xenografts are just not dense or pressurized enough, and it would be better to emphasize that tumor microenvironments affect drug delivery and aren't accurately modeled, which... sure, I suppose, though it seems like a nitpick.
3. Come on, you can't possibly think this is a valid criticism, and not just a thing you made up to have something to say.
> I continue to assert that the LLM's badly-plagiarising some papers, lecture notes and/or textbooks, blended with bad pop-sci analogies to the point of incoherence.
Then please, strive to do better!
I mean that in earnest, not just as an insult. You hate reading bullshit? Me too. If you're not familiar with the term "tumor architecture", it takes five seconds to put it into Google Scholar before you start insisting it's made up. Reducing the amount of bullshit on this site is everyone's duty.
> Mice usually clear drugs faster, not slower, than humans
… I knew that. That was one of the few things here I knew. But I read the LLM explanation and it looked right, so I started questioning other things instead, and got myself confused enough about basic anatomy that I didn't realise I was confused. (At one point, I decided that "blood goes through the liver and kidneys at the same rate as it goes through the heart" was a reasonable approximation, which is obviously false.)
And this despite that I was specifically watching out for LLM bullshit, and trying my hardest not to believe it. I guess this is evidence for my claim that LLMs are a terrible way for non-experts to learn about a topic, but wow, I was not playing the role in this argument that I thought I was.
> Maybe you're arguing that it's an oversimplification
Nope. That sounds like my genre of pedantry, but I didn't (and don't) understand the topic well enough to make that argument, so I wasn't. I was arguing that the description paints a picture of something unrealistic.
> Come on, you can't possibly think this is a valid criticism,
It's the criticism I fact-checked most thoroughly! So… yes, I just made it up to have something to say. (Honestly, the "just inject it near the tumour site" thing is extremely dubious, too: that would only work if you somehow eliminated blood flow through the tumour.)
> If you're not familiar with the term "tumor architecture", it takes five seconds to put it into Google Scholar
I put it into Internet Archive Scholar, forgot the quotes, and it just showed me machine-learning papers; so since I'd never heard of it before, I assumed the term was was made up. Lesson learned. (The term is much rarer than "tumour microenvironment" in the literature, but it does appear once on the Wikipedia page for tumor microenvironment, so I'm not sure how I missed it.) I can't figure out what the term actually means, but it does clearly mean something, and has done since at least 1971 (and probably earlier). doi:10.1136/bjo.78.11.871 sort of explains, but not really.
You mentioned textbooks in another comment. Do you have a textbook recommendation? I think I clearly need remedial study.
A great deal of effort and money is spent running studies. I'm inclined to assume the experts in the field are more aware of the tradeoffs of that decision and how to mitigate the downsides than probably all, but certainly the overwhelming majority, of people commenting on this thread.
Someone who needs to ask an LLM will not be helpful in trying to point out something they missed.
They're not pointing out something the researchers missed, they're pointing out something the people in this thread confidently hyping the results are missing. I'm certain the researchers are familiar with the limitations of the models they used (is it bad that the incentives of science and science journalism leads to overoptimistic coverage that hint at groundbreaking implications without explaining to lay readers what the unknowns are? Probably, but that's not these researchers' faults).
The average person in this thread, however, would probably be better informed by asking an LLM for context. They'd be even better informed by taking a few weeks to work through a textbook on cancer biology, but realistically they won't.
My horse in the race is that I'm annoyed by overenthusiastic comments that display a lack of understanding of the history of cancer treatment, and I'm going to be even more annoyed in a few months when the rounds of "haven't we had 1000 cures to cancer posted to HN??? why aren't we using any of them???" start showing up again. I'd rather encourage informed, skeptical optimism.
Targeted delivery of anti cancer methods is hard. Weather it is multiple radiation beams or anti-body cross linked chemo agents it’s never easy. Chemotherapy poisons the entire body but the cancer cells die faster. A generally administered compound that only affects cancer would be huge.
This is kind of true but misses the bigger picture. We have developed many drug options more targeted than traditional chemotherapy, famously Gleevec for example. The question isn't whether we've found one that could work at all, but how well does it work, what types of cancer it works for, and what the side effects are.
The result that it didn't affect any other cells really doesn't matter nearly as much when the other unaffected cells are literally from a completely different animal.
Literally reactive oxygen species targets cancer cell DNA. We are taking advantage of the unique chemical environment of the inside of a cancer cell and using it to generate oxygen in a double-whammy to destroy itself.
This is perhaps the best targeted method devised as it seems to collect basically entirely in tumors. Chemo and Radio therapy just aren't that targeted.
I lost my brother yesterday to cancer. I hope one day this can save lives. Go Beavs.
May peace be unto him, you, and the rest of your family.
When (if?) you feel ready, there is an organization [1] whose mission is to support siblings, parents, and grandparents of children who have died at any age. I have been heavily active with them since losing my only child 9+ years ago. I commend them to your attention. (Once again, when you feel ready.)
[1] compassionatefriends.org
<3 awful buddy
me too
I'm sorry you have to go through that. Speaking from experience.
> Go Beavs.
That's also Caltech's mascot!
Bernoulli the Beaver.
I never heard the “Bernoulli” part, new?
Yeah it was named a few years ago after a student/faculty poll https://tech.caltech.edu/2023/05/update-on-bernoulli-the-bea...
And MIT's!
Condolences to you, and your family. Hugs.
<3
<3
Hope this makes it to people soon. Have a family friend who was diagnosed with cancer a few days ago. It was here in Canada, so they offered her assisted suicide, literally within 30 seconds after telling her she had cancer. She didn't even really process the diagnosis before they were offering to help her die. They didn't offer to try any experimental medicine.
That's truly sick.
In the next 30 seconds you get ads for a coffin or a crematory. We're only trying to help you! Just like government itself is here to "help" us.
Were you actually there? Because that doesn’t sound very likely.
Not a comment on the parent post's situation, but MAID in Canada isn't quite turning out how it was promised. A recent report making a splash in certain circles pointed out that ~200 people in Ontario in 2023 got assisted suicide either the same day or the day after they filed their paperwork. The most notable case was a woman who, after submitting her paperwork, changed her mind and wanted hospice instead. However, she was denied hospice care and subsequently was put down.
Bit by bit, Canada risks defaulting to suicide over expensive care. That's not what people voted for when it was first proposed.
https://macdonaldlaurier.ca/wp-content/uploads/2025/02/MDRC-...
...because her spouse made an urgent request for MAiD and her spouse had medical POA...
The problem isn't that the urgent request went through, it's that she requested hospice or palliative care and was denied. And, let's be honest, POA should not be sufficient to euthanize a person who is awake, aware, and revoked consent.
"Do no harm" has been replaced with "put them down if it's cheaper and we can get away with it"
That's a separate problem from the parent post, and the point of my post was that her husband requested the decision on the assisted death, not the government.
I didn't mean to suggest that the government is going to hide under people's beds and stab them in their sleep if they get sick.
The government is responsible for funding every aspect of this process, though. It regulates the controls and rubrics over who gets what kind of care. The husband may have instigated it, but the system is broken if a person eligible for euthanasia isn't eligible for palliative care or hospice.
Most importantly, I continue to contend that MAID is turning into something that isn't what Canadians voted for. It is, however, turning into something that its opponents feared might come to pass.
Thats how I read it as well. The deeper issue is that he shouldn’t even be able to contact them when they deemed her lucid enough to not be eligible just a day earlier, especially when they were keen enough to notice he was burned out.
Separately, why do these services have to move so quickly? It seems like it’s either glacially slow in other countries where people pass before even finishing the paperwork, or insanely fast like in this case. There really should be a balance.
Who's involved that wants it to be less expensive? Surely the doctors don't care. In the US everyone wants it to be more expensive.
Since we're talking about Canada, ostensibly the government, as the provider of healthcare, wants it to be inexpensive enough that the citizens have a first-world level of care... as opposed to euthanizing sick people because it's easier than providing hospice or expensive treatment.
After all, using the monopoly power of government and taxation is meant to be more efficient and provide more services at lower costs.
A cynical person might presume that MAID is being used as a cost savings measure more than an empathetic alternative for those who do not wish to wait to die of natural causes.
Are the headlines the tip of the iceberg, or the exceptions that gain notoriety? When the government and health care system are so deeply intertwined, who has access to the data but not an incentive to obscure the facts? With any luck, time will tell.
Who in the US (that comprises "everyone") wants it to be more expensive?
Oh, mostly just the hospitals, the insurers, the medical device manufacturers, the pharmacy benefits managers, the pharmaceutical companies, the group purchasing organizations, and the clearinghouses. Everyone who can take a bigger cut if there’s more money sloshing around the industry.
Oh, well good then.
I think the point was this specific case is to most people probably murder.
That sounds like murder to me. I couldn't believe that and thought you must have been misrepresenting the facts. Nope, your summary is correct; the full case is there, in black and white, on page 22 of the Ontario Solicitor General's report, as you linked; and amazingly it was reviewed by a committee that didn't seem to find much wrong with it. That is very deeply disturbing. I have quoted the case overview below:
>CASE 4B Case Overview Mrs. B was a female in her 80s who had a challenging medical trajectory following coronary artery bypass graft (CABG) surgery. She experienced several post-operative sequelae, including wound dehiscence, osteomyelitis, and respiratory failure. She required specialized care in hospital, including additional surgical procedures. Due to physical and functional decline, Mrs. B elected for a palliative approach to care. She was discharged home with palliative supports (i.e., palliative care team and home care support services, including adaptive aids and personal support services). Mrs. B reportedly expressed her desire for MAiD to her family. In response, and on the same day, her spouse contacted a referral service on her behalf. The following day, a MAiD practitioner assessed her for MAiD eligibility. She reportedly told the MAiD assessor that she wanted to withdraw her request, citing personal and religious values and beliefs. She communicated that pursuing in-patient palliative care/hospice care and palliative sedation was more in-keeping with her end-of-life goals. The next morning, Mrs. B presented to the emergency department (ED) of her local hospital. Her spouse was noted to be experiencing caregiver burnout. Mrs. B was assessed to be in stable condition, and thereby discharged home with continued palliative care. Her palliative care physician completed a referral for in-patient palliative care / hospice care due to her social circumstances (i.e., caregiver burnout). Her request was denied for not meeting hospice criteria for end-of-life, and a long-term care application was offered.
On the same day, Mrs. B’s spouse contacted the provincial MAiD coordination service requesting an urgent assessment. A different MAiD assessor from the previous day completed a primary assessment and determined Mrs. B to be eligible for MAiD. The former MAiD practitioner was contacted. This MAiD practitioner expressed concerns regarding the necessity for ‘urgency’ and shared belief for the need for more comprehensive evaluation, the seemingly drastic change in perspective of end-of-life goals, and the possibility of coercion or undue influence (i.e., due to caregiver burnout). The initial MAiD practitioner requested an opportunity to visit with Mrs. B the following day to re-assess; however, this opportunity was declined by the MAiD provider due to their clinical opinion that the clinical circumstances necessitated an urgent provision. An additional MAiD practitioner was arranged by the MAiD coordination service to complete a virtual assessment. Mrs. B was found eligible for MAiD by this third assessor. The provision of MAiD was completed later that evening.
Vet and Paralympian spent four years fighting to get a wheelchair lift installed. Repeatedly offered medically assisted suicide instead.
https://indepnews.org/en/veteran-offered-suicide-instead-of-...
[flagged]
Experiencing cancer in my family I can tell for sure all of that buzz is quite exciting, but in the last 5 years there haven't been breakthroughs that would significantly improve outcomes for an average patient.
There have been massive improvements in treatments in the last 5 years. Sure, cancer is far from being "cured" - but survival today is far better than 5 years ago for many forms.
Among many others:
- CAR T therapy going from lab to oncology suite (first launch 2017, but use rapidly growing)
- Approval of Keytruda and similar for many additional forms of cancer (see the 2021-2026 milestones here: https://www.drugs.com/history/keytruda.html )
- Liquid biopsy going from lab to PCP's office - starting with Grail Galleri and moving from there (yes, the NIH results were weak, but the idea of a liquid biopsy at all would be laughed off 10 years ago)
- Move of Atezolizumab and Tecentriq from infusion (hour) to injection (minutes) to increase availability
- Lower dose CT scanning for lung cancer, including for non-smokers
And a long line of immunotherapies that are making the leap from lab to chair right now.
The last 5 years have probably been the most exciting in cancer research since the launch of the monoclonal antibodies in the early 2010s. There is still incredibly far to go, but the trend is in the right direction: https://employercoverage.substack.com/p/decline-in-cancer-mo...
I've heard that the improvements in cancer survival are mostly a statistical trick centered around earlier detection.
That people aren't actually living longer with cancer, they're living longer while we know they have cancer.
Is there any truth to that?
Short answer, no.
Long answer, it's a variable you need to consider when doing data analysis, and it depends on what exactly you're talking about, but it's absolutely not true for improvements in cancer survival general. One alternative method is to look at per-capita death rates, for example:
Reduction in US and UK childhood cancer death since 2000 https://ourworldindata.org/grapher/cancer-death-rates-in-chi...
Reduction in several countries' age-standardized breast cancer death since 2000 (Why did it increase in South Africa? I'm not sure, maybe socioeconomic factors) https://ourworldindata.org/grapher/breast-cancer-death-rate-...
Reduction in global age-standardized cancer death rate since 2000 (Scroll down to second graph. Since the population is getting older, age-standardization makes a fairer comparison) https://ourworldindata.org/grapher/cancer-death-rates
2000 is an arbitrary year I picked for clear visual changes without needing to haggle over statistics. If you want to feel optimistic, switch the childhood cancer death graph to 1960-now.
This method has different possible failure points. It could be that less people are getting cancer, or that people who would get cancer are dying of other causes, or reporting of cause of death has changed, though this is very unlikely for some figures, such as leukemia death rates for children in the US. Statistics is hard. Overall though, the evidence is very good that cancer survival has improved a lot due to better treatments since 2000.
If you have a more specific claim you're dubious about, I'd be willing to look into it for you. I'm very enthusiastic about this topic.
US life expectancy flattened out over the last 15 years, so I think that means all-cause-mortality is roughly flat per 100,000 too.
https://www.macrotrends.net/datasets/global-metrics/countrie...
Combined with your data, that implies that whatever wins we got from decreased cancer rates (e.g., less smoking) or improved treatment have been squandered elsewhere (probably obesity / heart disease).
If life expectancy had dropped over that time, then I guess it could be that cancer was as deadly as ever.
I wonder what the deal is with Greenland in your dataset. Lots of smoking? Lots of radiation?
I'm not exactly dubious about anything really, it was just something plausible I had heard a while ago and, while I don't recall where I heard it, I must have given it some credence for it to stick with me.
IIRC survival improvement has happened across all staging categories, including the worst one (IV, distant metastases found), so the answer would be "no".
A friend of mine, aged 50, has worked in pediatric oncology her entire (nursing) career. The ratio of surviving kids has flipped from 30/70 to 70/30 during her tenure.
Cool question. What form would an answer take? We need some detection benchmark data thats invariant over the period of interest. I hope the data exists but I would be surprised.
Another way to come at it would be mortality data. But that has a bunch of its own problems.
Everything is changing at once, it makes this kind of science so hard.
You seem to be knowledgeable on this topic.
What’s your prediction for the next five years?
mRNA vaccines to teach your body to destroy cancer cells
I just got nerdsniped for an hour writing up a comment about how cool they are.
https://xkcd.com/356/
mRNA cancer vaccines are the most exciting new treatment about to hit the clinic. Moderna's Phase 2b intismeran autogene randomized trial found a 49% (!!!) reduction in the risk recurrence or death for patients with high risk melanoma already on standard treatment. Several Phase 3 trials are underway. mRNA vaccines have the potential to work for a wide variety of tumors.
(95% confidence interval is 0.294-0.887, wide but not too wide, n=157, to be expected for phase 2).
How they work is also completely fucking insane. Intismeran autogene is personalized for every patient via sequencing their tumor DNA. That's sci-fi shit. If you're not impressed by that, you should be. Fast and scalable DNA sequencing, neoantigen identification, RNA synthesis, none of this is easy and all of it relies on recent innovations across multiple fields.
The first proofs of concept for personalized vaccines like this date back to 2017[1] or 2015[2]. The process for designing the vaccines requires a machine learning algorithm first published in 2020[3]. Details of the algorithm aren't available, but it validated against data published in 2019[4], and there have been many recent advancements in algorithms and datasets for biotech ML that it likely relied on. As you might already know, mRNA vaccines were first tested in humans around the 2010s[5].
[1] https://www.nature.com/articles/nature22991 [2] https://pubmed.ncbi.nlm.nih.gov/25837513/ [3] https://aacrjournals.org/cancerres/article/80/16_Supplement/... [4] https://pmc.ncbi.nlm.nih.gov/articles/PMC7138461/ [5] https://pubmed.ncbi.nlm.nih.gov/26082837/
> CAR T
it was available for [some] UCSF patients more than 5 years ago
Now its available to many standard patients and for more types of cancers. Thats huge progress.
It may feel that way due to the iterative nature of medical improvements, but over the past few decades there has been a consistent reduction in cancer mortality rates across most types of cancer [0]. Treatments really are getting better and more targeted. Immunotherapy has made huge breakthroughs. Combination treatments allow for significantly improved lifespans and better quality of life during treatments. There are a few cancers that remain hard to treat, but I have a lot of confidence that in the coming decades we will make strides in attacking them. That being said, I'm very sorry to hear about the pain you and your family must be going through. I've had a few close loved ones undergo cancer treatment and it was tough.
[0] https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac...
Examples aside, 5 years isn't long enough for a treatment to move from early mice trials to clinical use. The average time from application to FDA approval is about 10 years.
The breakthroughs happening now will benefit average patients later. It's frustrating, but it's not because we've run out of innovations.
Major breakthroughs of the kind you’re talking about are extremely uncommon. Instead it’s lots of little gains that keep adding up because cancer isn’t adapting overall people still get the same mutations they got 10,000 years ago.
So average person with cancer does better when any individuals cancer treatment improves and it keeps compounding over time. This doesn’t mean everyone with cancer gets a slight improvement, often it’s specific types or stages that improve without impacting others. Where general progress comes from is it’s not the same improvements year after year.
https://en.wikipedia.org/wiki/Timeline_of_cancer_treatment_d... I won't debate what merits a major breakthrough. I will say, that while there hasn't been any major developments in the past five years, I can't draw any conclusions from that tidbit of information.
That cuts out in 2015, but 5 year survival rates keep increasing with the USA just crossing 70%. Though across longer timeframes some of that is from early detection; even limited to late stage diagnosis the statistics still show significant improvement. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac...
What is the delivery mechanism for the MOF. The chemistry sounds promising (to this amateur, at least) but how does it get to and enter cancer cells?
It sounds like their method auto-accumulates in the cells because they're the only one with the right conditions to attract these chemicals?
(Having not read the article), most likely because the cancer cells (at least at more advanced stages) are busy trying to replicate as fast as possible, so they take up nutrients at a much faster rate than non-cancerous cells. As to why Iron in particular, it is used as a cofactor for enzyme and if Iron is a limiting factor for replication then supplying it will lead to a burst of growth which then (presumably by applying strong oscillatory magnetic fields) you can target those cells directly to locally boil them.
How do the iron nano materials get there? probably a combination of vasculature and diffusion.
They have done this kind of stuff before with gold nanoparticles, iron is a lot more abundant.
It seems like you could also help direct the iron to the tumor with magnets. That seems too simple to be true, but I don't see why it wouldn't be.
They should give it to some people with fatal stages of cancer.
I agree, or at least I would stress that people should be allowed to consent to that. I don't know what the prevailing medical ethics of doing that kind of thing in consenting patients in that state, but my uninformed intuition is I would disagree with it.
Though one thing that I might think researchers might not want is people may be too sick to recover even if their cancer disappeared tomorrow.
Both patient participation in clinical trials and compassionate use of experimental treatments are fairly common for cancer patients, with various accessibility barriers. (One issue with the latter, for example, is that the incentives aren't lined up for companies to provide unapproved drugs to dying patients, you're way more likely to get a horrible complication that leads to bad press than a miraculous recovery).
Here's an insightful blog series about Jake Seliger's experience participating in clinical trials. He was a regular HackerNews user who passed away in 2024: https://bessstillman.substack.com/p/please-be-dying-but-not-...
What is the success rate of a clinical trial? Just to see things in perspective.
It's around 10-15% for the whole drug I-III flow (13.8% according to [1]), but that varies dramatically based on therapeutic area. On the order of a third of infectious disease vaccines might be approved but only maybe 5% of oncology therapies because the latter often have a different standard for approval so it's cheaper to run trials.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6409418/
That's interesting, but I was talking about the success rate of someone with a terminal illness going the clinical trial route. Sorry, I now see that my question was not so precise.
For cancer, it doesn't seem to impact survival odds at all [1]. In other fields it may improve metrics a small bit but that's largely because in clinical trial patient selection, they're very careful to exclude anyone with an even remotely confounding factor (like weight/BMI).
[1] https://www.science.org/content/article/joining-cancer-trial...
This is why people begging to take untested, unknown drugs in the extreme off-chance of they work is generally a bad approach. It almost never works, and it encourages the earlier release of ineffective drugs to a wider audience.
If someone is about to die and you save them at the last moment, aren't you basically reviving a zombie at that point? He has eight new tumors. You can pop almost all of them and still be left with a terminal patient.
Even if you're buying time with every trial, all you've done is turn the patient into a lab rat for physicians to play around with. The ideal patient needs to be dead enough to have no human rights, but alive enough to participate in the trial. The hope of a miracle cure means the patient doesn't believe himself to be dead enough to not have human rights anymore. It's a paradox.
Signing the documents for such a trial is equivalent to signing your consent for euthanasia. It shifts the blame of death from the cancer to the company performing the trial. It's an extended form of organ donations where you donate your entire body while you're still alive.
Jake Seliger died ten weeks before his daughter was born. For many people, a chance at buying some time is worth a lot.
Trials are also by no means exclusively performed on terminal patients.
In the US, the FDA has a Compassionate Use exemption to clinical trials for exactly this circumstance!
There must be informed consent, no reasonable alternatives (which, in cases we deem terminal, is often the case), and some evidence pointing to the treatment possibly being helpful. It's an excellent ethical program that gives patients a choice and advances science.
In my experience most legitimate biotech companies working on promising drugs and therapies don’t want to touch the exemption with a 30 foot pole. Since they raise most of their money from the public to fund clinical trials, a single bad reaction could generate enough bad PR to derail fundraising and kill the drug. Sticking to clinical trials allows them to control that blast radius so even though the FDA approves >95% of applications, in practice very few drugs are available that way.
The biggest exception is oncology. Since everyone knows that chemotherapy is hell, cancer drugs tend to get a pass and pre-approval companies are (slightly) more willing to work with compassionate use exemptions.
Both of my parents have benefited from access to early medical trials. One is currently very late stage IV cancer. Access to trials is usually proxied through respected doctors/oncologists affiliated with major hospitals rather than offered broadly. I assume for reasons of experimental protocol and integrity the overseeing doctors are typically not the same as the conceiving research team.
That is exactly how clinical research works. My mother worked running clinical trials for two decades.
When she was diagnosed with leukemia she was able to get into a research study herself that gave us 10 more years together.
One of the horrible but necessary parts of trials is the control group, who receives placebo. This is only done in a few of the trial phases but is essential in measuring efficacy. If someone wants to throw their brainpower and a little bit of AI/tech at the problem, you could end up eliminating a lot of suffering.
AI and tech won't help, but if the threshold to try a drug were adjusted to exactly the right threshold, where enrolling in a study would be expected-value neutral (this is by marginal reasoning), taking a placebo would not be worse than not.
I'd think AI and tech could solve the problem pretty easily, assuming the study authors could get access to the health records of everyone that was not in the study (and could therefore generate control cohorts by looking at large samples of comparable patients outside the experimental group).
This is done for targeted advertising all the time. Frustratingly, the surveillance capitalism industry is precisely the reason the dataset you'd need probably shouldn't exist.
Maybe we'll get some decent lawmakers sometime soon, and problems like that will be fixed via legislation. They'd need to ban the root-cause of the problem. I'm guessing it's more likely the current congress will let private companies steal + sell everyone's info instead.
Well yeah, that's the plan. Every medicine needs testing in humans before going widespread. That's... how it always worked.
Actual paper: https://news.oregonstate.edu/news/new-cancer-killing-materia...
in mice?
Yes, in mice, but human cancer cells:
"When we systemically administered our nanoagent in mice bearing human breast cancer cells, it efficiently accumulated in tumors, robustly generated reactive oxygen species and completely eradicated the cancer without adverse effects ..."
So it kills human cancer and doesn't harm the mouse in the process.
Xenografted human tumors in mice != human cancer. The support structure of the tumor (tumor microenvironment) differs between model mice and humans, cells derived from human cancer that can be cultivated in a lab and xenografted differ from typical human cancer cells, and xenografting requires immunodeficient mice, just to name a few factors that affect treatment response.
Mice models of cancer are useful, but you should never be too surprised when something that works in mice doesn't work in the clinic, xenografting or no. Cancer is complicated.
Doesn't harm the mouse. But would it harm the normal human cells?
Human breast cancer, in mice.
If it worked, how much might it roughly cost per treatment, at scale?
Actually, when in the lifecycle of developing a treatment does anyone have a real idea of what cost will be? Can anyone know this yet?
In terms of where _prices_ are set, that negotiation is a function of efficacy relative to other things in the market right? If it ends up treating cancers that each already have a reasonably effective treatment, maybe the pricing isn't that high -- but if it is effective in cases where currently there are no options, the price should be high?
But for something that potentially works against a range of cancers, should we expect to see a sequence of more specific trials (i.e. one phase 1 for basic safety, a bunch of phase 2s for efficacy on specific cancer types, a sequence of phase 3s in descending order of estimated market value? And in 10 years, Alice and Bob with different cancers will pay radically different amounts for almost exactly the same treatment but with small variations in some aspect of the formulation so they can be treated as distinct products?
Pharmaceutical companies don't just fund research without having a model of the expected costs to bring something to market, the expected market size, and the viability and cost effectiveness of other potential treatments.
They have entire teams of people who figure out the viability and pricing of therapeutics before the first dollar is spent, with estimates getting refined the further you get along in the cycle.
I have no idea whether this is real, nor do I know how the concentration compares with that used in the study, but https://www.nanominerals.co.uk/products/the-health-factory-n... advertises it as a supplement (not as a medicine) for $40/ half liter.
(The ad also claims that the water their iron is suspended in is "energized", which makes the rest of the ad seem...questionable.)
As far as nanomaterial assembly goes MOF syntheis is pretty scalable
Does the cost matter? Many countries subsidize healthcare, so there's either no charge or a token payment which doesn't even pretend to cover the cost of treatment.
Other countries use insurance, so once again the end cost is essentially irrelevant.
Yes? Countries that subsidize healthcare don't calculate infinite value per person.
The cost absolutely matters. If something costs tens of thousands of € per month for a long time then it will either not be approved or will be used very rarely. The cost is not irrelevant because the insurance does not have infinite money. They need to decide which cures, medicines, operations they fund. They can spend 1000€ to cure 100 people of something or to spend 100k to maybe cure someone with an experimental treatment.
This is one of the issues with the modern cancer cures, thst they are very specific to the cancer, the patient, need one off lab work for each patient and this makes them very expensive and not affordable to many. Despite having public healthcare the managers of it still need to decide what to spend their limited funds on.
The treatment cost for the newest hep C drugs have dropped dramatically since they were introduced. Started around $100,000 for a course. So six-figure price tags don't keep "cure"-level drugs from getting approved or introduced. The cost of the existing not-a-cure treatments also added up fast, after all; as they do for many cancers.
You're right about the specificity - Hep C is a bigger-population target than a lot of cancers are - but a lot of the new approaches are looking to be inherently more "personalized" to compensate.
Of course it does. Countries have budgets. Expensive drugs aren't doled out like candy; they require screening, waits, connections, and even bribes.
> Other countries use insurance, so once again the end cost is essentially irrelevant.
I think it matters because oftentimes insurance companies won't cover treatments if a cheaper form of treatment exists. It doesn't matter if the old treatment is less effective or a much worse outcome for a patient. This is especially true for "new" treatments.
Cost is always relevant, given that the amount of money in any healthcare system is limited and someone must decide whether to pay for patient A or patient B.
That sounds extremely promising
[flagged]
The people that want to prompt an LLM will do it.
These are all correct observations about the limitations of xenografted mouse models.
No, they aren't: the second is irrelevant and unphysical. Highly-pressurised cores? Really? "Dense", I could buy, but:
• If there's blood supply, then (A) it can't be a much higher pressure than the blood pressure (unless there's some Rube Goldberg machine involving active transport), and (B) the tumour is reachable by treatments like this;
• And if there isn't blood supply, then the tumour's core is necrotic, and a treatment to kill the dead cells wouldn't do anything anyway. (Sure, killing the tissue that isolates a lump of necrotic flesh from the rest of the body might cause new and exciting problems, but somehow I think those might be preferable to incurable breast cancer.)
The second is just not a relevant criticism. The third, if it's an actual issue, can probably be worked around by tweaking the molecule slightly – and if not, suppressing the immune system isn't that difficult (it's a known side-effect of many chemotherapies). The first, if it's an issue, can be avoided by injecting the medicine near the target site.
I agree that this treatment might not work in humans, but all the AI's done is taken a generic list of potential concerns, and inserted technobabble to try to make it match the scenario. If you want generic criticism, see https://news.ycombinator.com/item?id=47209076: at least that's true.
You're incredibly wrong. You also cited my own comment at me.
The problem of high interstitial pressure (not blood pressure) interfering with drug delivery in tumors is basic cancer biology. If you don't believe me, here's:
A review published in a reputable oncology journal, with over 100 citations, entirely about targeting interstitial pressure, with an abstract leading with "Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment." https://aacrjournals.org/cancerres/article/74/10/2655/592612...
Another review, also a reputable oncology journal, 1000 citations, about tumor stroma more generally, which lists high interstitial pressure as a mechanism by which tumors limit drug access and includes a nice diagram (Figure 2a). https://www.nature.com/articles/s41571-018-0007-1
That's how basic this fact is. 1000 citation reviews in Nature have beautiful fucking diagrams of it. I'm pretty sure it was in the textbook of my undergraduate biology class.
If you don't know shit, don't talk shit. People will criticize LLMs for being overconfident while writing essays from their ass.
I did briefly consider that this was referring to intercellular fluid, but "highly pressurized cores" is a terrible way to describe high IFP, so I rejected that interpretation. I thought the LLM was "trying to" refer to some kind of dense-walled cyst. (Of course, the LLM wasn't actually trying to say anything at all.) (And I think my argument there about osmotic pressure, oxygen diffusion and tissue necrosis is correct: hypoxia's already an issue for tumours, and there are only so many heroic workarounds available before a cell's only option is to die; and since blood pressure is higher than even the high IFP found in tumours, that's the appropriate bound for the argument I made.)
Your interpretation leaves the LLM's discussion of stroma as a non-sequitur, since that is not why high IFP causes problems for drug uptake; and at that point, I think you're just substituting a correct statement in place of the LLM's superficially-meaningful nonsense. I'll go through it again, this time focusing on the names assigned to each point:
"1. The Scale of the Human Body" talks about the excretory system. The part of the explanation comparing "tiny" to "vast" is at the very least misleading, but I would call it outright wrong. And yes: I am also thinking of all those "well actually, the geometry of the circulatory system" interpretations that make it technically correct, but… if a biology teacher explained it like this, would you really think they were teaching it properly? (I mean, seriously, calling "The human liver, spleen, and kidneys" "the reticuloendothelial system"‽)
"2. Tumor Architecture", under your charitable interpretation, isn't talking about "architecture" at all.
"3. Immune System Differences" is at least named right; but a treatment that only works in immunosuppressed patients is still a treatment. You could imagine a cancer drug sufficiently-effective that it is worth suppressing the immune system just so you can administer it. (I don't think it's likely that this is one, but that's for experiment to decide. And if the patient's immunocompromised anyway…)
> You also cited my own comment at me.
Oops. That does make me feel foolish. In my defence: it didn't occur to me that anyone could think you were saying the same things as the LLM, because what you were saying was correct, and what the LLM was saying was nonsense.
Although, if you thought you were saying the same thing… is the LLM's "tumor architecture" supposed to refer to the tumour microenvironment‽ That would explain the stroma mention, but… wow that is not a sensible way to say that. I continue to assert that the LLM's badly-plagiarising some papers, lecture notes and/or textbooks, blended with bad pop-sci analogies to the point of incoherence.
Funnily enough, now that I've gone back and reread the LLM's explanations, I've decided that point 1, the one you were least critical of, is garbage whereas points 2 and 3 are fine.
1. Mice usually clear drugs faster, not slower, than humans, so either point 1 is wrong or I'm missing something, and either way it's a bad explanation.
2. This point is fine. The use of the phrase "tumor architecture" in this context is common, for example this random paper https://www.cell.com/cancer-cell/fulltext/S1535-6108(12)0008... and several papers cited by the Nature review. I don't get your problem with the phrase "highly pressurized cores" is, or what you're calling a non-sequitur.
Maybe you're arguing that it's an oversimplification to imply that xenografts are just not dense or pressurized enough, and it would be better to emphasize that tumor microenvironments affect drug delivery and aren't accurately modeled, which... sure, I suppose, though it seems like a nitpick.
3. Come on, you can't possibly think this is a valid criticism, and not just a thing you made up to have something to say.
> I continue to assert that the LLM's badly-plagiarising some papers, lecture notes and/or textbooks, blended with bad pop-sci analogies to the point of incoherence.
Then please, strive to do better!
I mean that in earnest, not just as an insult. You hate reading bullshit? Me too. If you're not familiar with the term "tumor architecture", it takes five seconds to put it into Google Scholar before you start insisting it's made up. Reducing the amount of bullshit on this site is everyone's duty.
> Mice usually clear drugs faster, not slower, than humans
… I knew that. That was one of the few things here I knew. But I read the LLM explanation and it looked right, so I started questioning other things instead, and got myself confused enough about basic anatomy that I didn't realise I was confused. (At one point, I decided that "blood goes through the liver and kidneys at the same rate as it goes through the heart" was a reasonable approximation, which is obviously false.)
And this despite that I was specifically watching out for LLM bullshit, and trying my hardest not to believe it. I guess this is evidence for my claim that LLMs are a terrible way for non-experts to learn about a topic, but wow, I was not playing the role in this argument that I thought I was.
> Maybe you're arguing that it's an oversimplification
Nope. That sounds like my genre of pedantry, but I didn't (and don't) understand the topic well enough to make that argument, so I wasn't. I was arguing that the description paints a picture of something unrealistic.
> Come on, you can't possibly think this is a valid criticism,
It's the criticism I fact-checked most thoroughly! So… yes, I just made it up to have something to say. (Honestly, the "just inject it near the tumour site" thing is extremely dubious, too: that would only work if you somehow eliminated blood flow through the tumour.)
> If you're not familiar with the term "tumor architecture", it takes five seconds to put it into Google Scholar
I put it into Internet Archive Scholar, forgot the quotes, and it just showed me machine-learning papers; so since I'd never heard of it before, I assumed the term was was made up. Lesson learned. (The term is much rarer than "tumour microenvironment" in the literature, but it does appear once on the Wikipedia page for tumor microenvironment, so I'm not sure how I missed it.) I can't figure out what the term actually means, but it does clearly mean something, and has done since at least 1971 (and probably earlier). doi:10.1136/bjo.78.11.871 sort of explains, but not really.
You mentioned textbooks in another comment. Do you have a textbook recommendation? I think I clearly need remedial study.
A great deal of effort and money is spent running studies. I'm inclined to assume the experts in the field are more aware of the tradeoffs of that decision and how to mitigate the downsides than probably all, but certainly the overwhelming majority, of people commenting on this thread.
Someone who needs to ask an LLM will not be helpful in trying to point out something they missed.
They're not pointing out something the researchers missed, they're pointing out something the people in this thread confidently hyping the results are missing. I'm certain the researchers are familiar with the limitations of the models they used (is it bad that the incentives of science and science journalism leads to overoptimistic coverage that hint at groundbreaking implications without explaining to lay readers what the unknowns are? Probably, but that's not these researchers' faults).
The average person in this thread, however, would probably be better informed by asking an LLM for context. They'd be even better informed by taking a few weeks to work through a textbook on cancer biology, but realistically they won't.
My horse in the race is that I'm annoyed by overenthusiastic comments that display a lack of understanding of the history of cancer treatment, and I'm going to be even more annoyed in a few months when the rounds of "haven't we had 1000 cures to cancer posted to HN??? why aren't we using any of them???" start showing up again. I'd rather encourage informed, skeptical optimism.
Targeted delivery of anti cancer methods is hard. Weather it is multiple radiation beams or anti-body cross linked chemo agents it’s never easy. Chemotherapy poisons the entire body but the cancer cells die faster. A generally administered compound that only affects cancer would be huge.
This is kind of true but misses the bigger picture. We have developed many drug options more targeted than traditional chemotherapy, famously Gleevec for example. The question isn't whether we've found one that could work at all, but how well does it work, what types of cancer it works for, and what the side effects are.
Command-F "mice"
yup. every time
Yes, but they were human cancer cells.
The result that it didn't affect any other cells really doesn't matter nearly as much when the other unaffected cells are literally from a completely different animal.
Will this be buried like rest if cancer cures?
Anything that doesn’t genetically target cancer cells is just not the solution long term. Any progress is good though.
Literally reactive oxygen species targets cancer cell DNA. We are taking advantage of the unique chemical environment of the inside of a cancer cell and using it to generate oxygen in a double-whammy to destroy itself.
This is perhaps the best targeted method devised as it seems to collect basically entirely in tumors. Chemo and Radio therapy just aren't that targeted.