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I lost my brother yesterday to cancer. I hope one day this can save lives. Go Beavs.

> Go Beavs.

That's also Caltech's mascot!

Bernoulli the Beaver.

And MIT's!

I'm sorry you have to go through that. Speaking from experience.

<3

<3

<3 awful buddy

me too

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.

Were you actually there? Because that doesn’t sound very likely.

Uhuh. Sure.

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...

> 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.

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.

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.

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.

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.

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/

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/

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...

That sounds extremely promising

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...

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.

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.

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.

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.

Yes? Countries that subsidize healthcare don't calculate infinite value per person.

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.

> 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.

Of course it does. Countries have budgets. Expensive drugs aren't doled out like candy; they require screening, waits, connections, and even bribes.

Command-F "mice"

yup. every time

Yes, but they were human cancer cells.

[flagged]

The people that want to prompt an LLM will do it.

These are all correct observations about the limitations of xenografted mouse models.

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.

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.

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.

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.