Comment by ramraj07 | Hacker News Reader

Comment by ramraj07 | Hacker News Reader

Original article - https://www.nature.com/articles/s41590-019-0578-8

Very interesting finding indeed, these T cells seem to (not fully confirmed) target cells with abnormal mrtabolism, which is one of the hallmarks of cancer in general (most cancers at least).

This solves one of the biggest problems with immunotherapy, which is that if a cancer is not different from regular tissue in any fundamental way that the immune system cannot recognize, then it can't fight it. This is why melanoma is the poster child of immunotherapies (skin cells get mutated a ton due to UV so skin cancer has a lot of mutations to differentiate it by). If this cell stands further scrutiny, it could potentially be a very general therapy option indeed.

Potential caveat is that cancers typically find a way to generate resistance, and markers of abnormal metabolism (at least as detected by this MR1 receptor) night be easy to suppress, in which case this might just become one in a line of multiple treatments. That might still be good enough though.

> cancers typically find a way to generate resistance

Resistance is a neat thing.

I remember (and I'm sure someone will reply with a link to it, since I can't find it) reading a story about a fellow with a very seriously antibiotic resistant bacteria infecting his chest. It resisted everything they had. Researchers found a phage that would attack that specific bacteria- but alas, the bacteria became resistant to the phage as well!

Fortunately, the bacteria had limited dimensions in which to change. The changes needed to become resistant to the phage made it no longer resistant to at least one of the antibiotics. It could not have its cake and eat it to. With both attacks against the bacteria ongoing, it was defeated.

What I'm implying with all this is that yes, the cancer may become resistant to this therapy in question but in doing so it may be forced to become less dangerous, or less resistant to other forms of attack. It does not change merely from "not resistant" to "resistant" but from "form A, which is not resistant" to "form B, which is resistant", and "form B" may have a lot of other consequences.

Stuff like this gets used in cancer treatments, too, with combination therapies [1].

Even more interesting are drug holidays: cancer becomes resistant to drug A by evolving a new clone that uses some other metabolic pathway unaffected by the drug but is less efficient. Stop drug A, the first more efficient clone takes over again. Give drug A again and there is no resistance for a while.

[1] https://www.oncode.nl/news/one-two-punchmethod-published-in-...

It’s my understanding that cancer stems from malfunctioning of our own cell processes, rather than from something that is viral/bacterial.

For that reason it seems wrong to think about cancer as “developing” resistances - I don’t believe that cancer is something that evolves/mutates.

Turns out I’m wrong! Cancer does undergo natir selection and develops resistance:

https://en.m.wikipedia.org/wiki/Somatic_evolution_in_cancer#...

and they can be viral in nature, see oncogenic viruses e.g. HPV (cervical cancer)

It's true that cancer is made of human cells but it can still evolve on it's on. Evolution applies to anything that can reproduce while making small changes between generations. Cancer cells do this better than healthy ones, at least within the time scale of a single human life. In some species cancers have even evolved to become contagious and a single tumor has spread to thousands of hosts. https://en.wikipedia.org/wiki/Canine_transmissible_venereal_...

Evolving is how it became a cancer in the first place.

I'm kind of curious why those priors led you to this conclusion, as I can't follow it at all. I understand that you have already figured out that it is wrong, but I'd like to understand what made you arrive at the wrong conclusion in the first place.

I always wondered, resistance is an energetic cost as it tends to disappear without constant selection pressure. Why not infect someone with the non-resistant strain, let it outcompete the resistant strain inside the body and then kill it with antibiotics?

In general the patient is only being treated because the infectious agent is doing some kind of damage (makes them sad/sick/dead...) So the fear is that before the non-resistant strain has supplanted the resistant one the patient has become too (sad/sick/dead)

Can you link to this phage paper please. I'm about to start a project looking at phages.

https://www.vox.com/future-perfect/2019/5/14/18618618/phage-... is not the one in remembering, but it mentions the same effect.

> deploying phages can cause the bacteria to evolve in response, and that evolution sometimes involves switching from being antibiotic-resistant to being sensitive to antibiotics.

There's a few big stories like this. Chances are, in the next 25 years you may find yourself being treated with phages.

> which is one of the hallmarks of cancer in general (most cancers at least)

It may well be the definition factor, at least some people think so: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/

If I remember their argument correctly, cells that "only" reproduce anarchically present little danger (benign tumor) if they don't also do so at an abnormally fast rate / metabolism.

Most cells stay in the same place, die when told to and don't make more copies. Necessarily some of your cells don't obey one or more of these rules (you wouldn't last long if your blood cells weren't endlessly copied for example or if they stayed in one place). But if all three rules get broken you've got cancer.

The cancer I had when I was young, Hodgkin Lymphoma, is one extra rule broken because the lymphatic cells already don't stay in one place and makes extra copies of themselves - which is why it relatively often occurs in young people. One copying error and the "Die when told to" feature breaks in the new copies and now you've got cancer.

Sorry but this is just false. Everyone has "cancer" all the time because these "mistakes" happen all the time. The reason why someone gets the medical condition, "cancer", is because for some reason, the immune system stops cleaning up these rouge cells. That could be a huge infection or injury, general decay of your body, etc, causing a cancer clump to form. Once cancer reaches a certain size, it will develop mechanism, like acidity, that will inhibit immune response regardless of whether the immune system would now classify the cancer as a threat. In any event, cancer is a very complicated condition, with many different causes. It's unlikely there will be a one-size-fits-all solution.

This is true for most stationary cancers before they turn malignant.

Immune cells are already resistant to each other, and especially to stress. Additionally, they have pieces of genetic code that are manipulated during their life and potential to become self-reactive with no activation. If they lose anergy and apoptosis, it can be enough, and there are many paths to activate them into mitosis.

Immune cells can become a cancer just by their number and statistics of error. Just big leukemia is but a symptom but has potential for first stage cancer.

Well the position being discussed, different from the current consensus, is that what sets apart the "cancer" condition from routine mutated cell line is metabolism, not immunity to the immune (!) system.

In that spirit, subsequent mutations that confer resistance can be seen as a consequence of this abnormally high metabolism rate that overwhelm the system and also cause increasing mutation rates.

In conclusion, while cancer may indeed become a complicated condition to treat, the root cause thus defined is rather simple. Whether this paradigm is valid and useful is an open question, but the article being discussed sure seems to point that way.

"If I remember their argument correctly, cells that "only" reproduce anarchically present little danger (benign tumor) if they don't also do so at an abnormally fast rate / metabolism."

Forgive this (very tortured) analogy, but I think there is a lesson here for would-be extropians who think society will simply tolerate a few vampires here and there.

Specifically: they'd better be living lives of quiet, impoverished contemplation ...

> Potential caveat is that cancers typically find a way to generate resistance

It's randomness. Theoretically speaking every possible combination could happen. So you should be able to have a Cancer cure, a cancer resistant to that, another cure, another cancer, etc.. at least until you cover all of the possibilities.

The goal is to have science become faster than physical mutations. You generate medicines faster than you generate resistant mutations.

It's randomness with causality; each momentary mutation may be random, but that mutation must be possible based on the prior state. So while it may be possible (even probable) for a perfectly resistant cancer to exist, it's much less likely for a causal chain to exist that allows for that.

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