Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

Our L1 defense is actually incredibly good. A human will undergo about 10^16 cell divisions over the course of their lifetime. Around 10^3 to 10^6 of those divisions will result in a mutation that gets past the L1 defenses and need to be eliminated by the T cells. It's not generally easy to make dramatic improvements to something with a 99.9999999% success rate.

The immune system is pretty good too, which means any given improvement to the replication system is, all else being equal, probably going to prevent mutations the T cells would already handle. If you need to do the research to figure out what's getting past the immune system anyways, and improving the immune system is lower hanging fruit, it's the logical place to start.

This is a fascinating niche of evolutionary biology that I have worked in for a while. The short answer is that yes, as far as we can tell all organisms evolve increasingly more efficient replication machinery, however at some point the strength of selection is no longer powerful enough to overcome the strength of genetic drift and some degree of error rate persists. As far as we can tell it seems like population size governs where this balance ends up such that small populations have high mutation rates and large populations have reduced mutation rates. Michael Lynch coined the term drift barrier hypothesis to describe this phenomenon. https://pubmed.ncbi.nlm.nih.gov/23077252/

L2 is being prioritized because our L1 defences are already very good. We are a long-lived species, and our natural ability to fix errors is so good that it is hard to improve upon. Maybe the long-lived tortoises or whales can do it better, maybe. But we have "several nines of reliability" there.

OTOH our L2 isn't that good, mammals in general (with some notable exceptions such as bats, whales and naked mole rats) are prone to cancer in their older age. There probably is a lot of relatively low-hanging fruit there.

If you think about it - individual cells aren't very precious and if some of them gets FUBARed by something (a virus, radiation or chemical insult), it is better to whack it and reuse the proteins to build a new one, if possible, instead of wasting time and resources on reconstruction of a total wreck.

Which also means that some research into replenishment of stem cells is necessary - and this is, IMHO, the really underfunded part of the whole thing. We lose a lot of stem cells as we age. Maybe we don't have to.

It starts with mutations (sometimes accelerated by mutagens (smoke, alcohol, etc) or inflammation (viruses, infections, etc) or just chance (things like asbestos up the division rate by constant physical damage and thus up the probability or an error in copying).

But there is much more to it. This is a nice paper for an overview: Hallmarks of Cancer (tng) [0]. It (among others) adds the very important and for years underestimated role of the immune system to the original 2000 paper.

[0] https://www.cell.com/fulltext/S0092-8674(11)00127-9

While cancer is caused by mutations in the genome, these mutations in turn produce the unifying property of cancer: unchecked cell replication.

Most cell types have systems to safely manage replication. Broadly, there are gas pedals (oncogenes) and brakes (tumor suppressors). A classic oncogene is something like RAS, which activates a signaling cascacde and stimulates progression through the cell cycle. A canonical tumor suppressor is something like TP53, the most frequently mutated gene in cancer, which senses various cellular stresses and induces apoptosis or senescence.

Most cancer genomes are more complicated than individual point mutations (SNPs), insertions, or deletions. There are copy number alterations, where you have > or < 2 copies of a genomic region or chromosome, large scale genomic rearrangements, metabolism changes, and extrachromosomal DNA. There is a series on the hallmarks of cancer which is a useful overview [1].

All of the mechanisms that intrinsically regulate cell growth would fall under your "L1 defense". Unfortunately, the idea of reversing somatic point mutations is likely to be a challenging approach to treating cancer given the current state of technology.

First, for the reasons above, cancer is often multifactorial and it would be difficult to identify a single driver that would effectively cure the disease if corrected. Second, we don't have currently delivery or in vivo base editing technology that is sensitive or specific enough to cure cancer by this means. There are gene therapies like zolgensma[2] which act to introduce a working episomal (not replacing the damaged version in the genome) copy of the gene responsible for SMA. There are also in vivo cell therapies like CAR T which attempt to introduce a transgene that encodes for an anti-cancer effector on T cells. These sorts of approaches may give some insight into the current state of art in this field.

Edit: also I should note that the genes involved in DNA repair (PARP, BRACA1/2, MSH2, MLH1, etc) are frequently mutated in cancers and therapeutically relevant. There are drugs that target them, sometimes rather successfully (e.g. PARP inhibitors). But the mechanisms of action for these therapies are more complicated than outright correcting the somatic mutations.

1. https://aacrjournals.org/cancerdiscovery/article/12/1/31/675... 2. https://en.wikipedia.org/wiki/Onasemnogene_abeparvovec

Cancer sucks and I wish your father the best.

Also not a doctor or microbiologist, but just wanted to share my layman’s guess on why fixing enzymes will not completely solve the issue: there’s 2 strands of DNA and to fix the broken (mutated) strand you need to have one correct template strand intact so you know what it should be fixed into. It could be the nucleotides swapped places between strands or are deleted completely or otherwise both mutated, which would mean any repair will not revert the sequence to what it used to be.

The other comments so far are probably more informed.

The catch is that there are thousands of promising therapies in animal models/pre-human testing. A very very tiny fraction of them will ever make it to market for a variety of both good and not-good reasons.

Very small sample size and only in mice. Most experimental treatments don't make it to the clinic, and this could be another in a long list of exciting early results that don't lead to anything. However... These results seem too good to be true, but the paper actually seems pretty good. There have been other attempts to use anaerobic bacteria to treat cancer (as solid tumors tend to be hypoxic environments), this is the first I've seen that interacts with PD-1/PD-L1 pathway. This is the most promising cancer treatment I've seen in quite a while. Maybe we can be cautiously optimistic!

Certainly good news for mice.

I wonder if anyone has tried to engineer a mouse that lives forever by applying all these life enhancing mouse therapies at once.

A few years ago we also had 100% effective medication with zero side effects. Now birth rates are down, mortality up, and young people misteriosly die from cancer and hearth attacks.

I hesitate to link directly to a single podcast dealer, but if you search for Dave Ricks, CEO of Eli Lilly's podcast with Stripe brothers, there's some alpha in there.

Yes it is amazing! Solid tumors tend to be poorly oxygenated, as they don't have a good network of blood vessels to supply them. The bacteria in these experiments can only live in low oxygen environments, so they will multiply in the tumor and die in any other part of the body they end up in. It's a clever idea, hopefully it will be successful.

Even lay-er person, but maybe the specificity is not that impressive in mice? Perhaps when you scale to more complex animals it is inevitable to see false positives (detrimental effects to healthy cells)?

https://www.tandfonline.com/doi/full/10.1080/19490976.2025.2... Link to the research article. Are you referring to the news release?

Still the idea is beautiful. Since tumors are oxygen-deficient and suppress the immune response, anaerobic bacteria would proliferate there, and wreak havoc, while in the healthy parts of the organism they would be rapidly eliminated. Additionally, since the bacteria accumulate in the tumor, and the immune system has just responded to their invasion, T-cells will flock to the tumor, destroying what remains of it in due course.

As they say, "the fame of a mathematician is measured by the number of poor papers", because pioneering works are often awkward, treading completely unknown ground. Maybe the same applies to biology sometimes?

Figures 2 and 3 seem to be different experiments, with n=3 and n=5, respectively. Both showed 100% survival. Obviously very small sample sizes, but still promising.

Yes in figure 2 it's 3 mice, next figure 3 they also have 5 (panel e)

In case people don't want to click on a random link, it is actually quite interesting:

Crocodile blood antibiotics hope

Scientists are catching crocodiles and sampling their blood in the hope of finding powerful new drugs to fight human infections.

Even horrific fighting wounds on the animal heal quickly

I'm not a doctor, but in some fairness, I think there has been a lot of progress in chemotherapy and radiation. "Increasing 5-year-survivability by 0.5%" doesn't make a fun sexy headline, but that's still an achievement that required a lot of hard work and enough of those happening still adds up.

I agree with your overall point though; it's a little annoying that every few weeks we hear about a new experiment that seems to indicate that we'll have a radically new and effective form of treatment for cancer only for it to never materialize.

Yes, you only hear about the initial breakthrough. The regular news doesn't report the trials unless things go spectacularly wrong. And you don't hear about the successes using the therapy on patients where traditional treatments didn't work. And you don't hear about the treatments successful enough that they replace the traditional treatments. But they are there, being used and saving lives. A family member's prostate cancer metastasized after 20 years of hormone therapy, they refused chemotherapy, and had their life saved by radioligand therapy, a treatment not available just months earlier. No side effects beyond a dry mouth, and now off the more debilitating hormone treatments.

There's also AIDS that I heard have been practically cured. Since then I have became less pessimistic about drug progress

Keytruda (pembrolizumab) has been pretty monumental.

In my dad’s case- he had gastric melonama. We surgically removed it and as consolidation We administered pd-L1 Immune checkpoint inhibitor. Melonama recurred again in 6 months time. This time in esophagus.

As an engineer I think all drugs tested and efficacies studied are on statistically not so significant data points. Given the permutations and combinations far exceed the clinical trials available and hence everything post clinical trial is also just an extended trial.

Wonder How to fix this? I am assuming heLa cells etc are also not the right test setup to have better test results.

Seems like a very interesting approach, even if it’s early stage.

> Many tumor types are not PD-l1 positive. > Doxy is an ancient SOC chemo. This is a nothing burger.

Meh the research didn’t say those were state of the art, but that they were “common” treatments. In other words a baseline for a presumably cheap and well studied animal surrogate.

> CAR-T is ahead of the game, and will be the ultimate winner here as it grows to scale.

Last I read up on it last year CAR-T treatments struggled with solid mass tumors.

Many cancers don’t have unique proteins for CAR-T to target (similar to the pd-l1 issue).

Then CAR-T struggles getting the modified T cells into the solid mass tumors en masse. Interestingly this approach actually makes use of the tumor environment rather than be hindered by it.

As a rule of thumb, it’s best to assume that all studies like this are in mice or rats unless the headline specifically says “in human trials”.

Murine studies are a dime a dozen and therefore it’s the default assumption when reading research papers. When human trials commence the fact that it’s in humans is a big part of the research and therefore paper titles.

I would be in favor of adding a standardized [in mice] to the titles of all HN submissions about medical breakthroughs. Most of them end up being in mice and many do not reproduce in humans. It would help, at a glance, to know how significant a study's results are.

Thanks, we've inmiced the title.

Of course it was done in mice, tests with animals are obviously mandatory before human trials.

They've given more lives to humanity than humanity itself (j/k)

Ah, I was wondering if it was one of those. And of course there's a relevant xkcd [0]

[0] https://xkcd.com/1217/

I know hearing this gets old, however, please review sources outside of LLMs for accuracy. LLMs take a whole bunch off stuff from all over the internet and distill it down to something you can consume. Those sources include everything from reddit to a certain de-wormer that folks still think treats COVID (side note: I've a few long COVID victims in a support group I am in, and they are not happy about the disinfo that was spread, at any rate)...LLMs/"AI" does not and cannot innovate, it can only take all existing information it knows, mash it all together, and present you with a result according to what the model is trained on.

I'm not against AI summaries being on HN, however, users should verify and cite sources so others can verify.

However, I'm just a normal nerd that wants to fact check stuff. Perhaps I'm wrong in wanting to do this. We'll see.

> Could it be that this organism switches to anaerobic respiration when it finds itself inside cancer tissue

Unlikely. The leading hypothesis is that mitochondria are a part of the apoptosis cycle, so cells need to disable them to become cancerous. This is called the Warburg effect.

There are several drugs that target this mechanism, inhibiting the anaerobic metabolism. They are effective initially, but cancers always find ways to work around them.

I'm happy to wait for the experimentation to weigh in for this one dawg

"according to Gemini" ........

aCcoRdinG To gEmiNi

Need the what now?