6 ms·

Sadly, I agree 100%. Time and again I see labs/papers/companies trying to "target" cancer cells for specific killing. What we are all awaking up to now in the f

Sadly, I agree 100%. Time and again I see labs/papers/companies trying to "target" cancer cells for specific killing. What we are all awaking up to now in the field is the only way to reliably achieve durable responses you need to a) have a functional immune system, b) somehow convince it to kill cancer cells via surface antigen recognition/MHC all without getting checkpointed. It's a super fucking hard problem and I makes me so angry; but I agree there is a bit of awe in how clever/sneaky/insidious it is.

space_fountain 5y ago
I’m not a biologist, but how I imagine it is that cancer is just evolution + entropy. We can obviously get a lot better at controlling it, but it will always be there because there’s always a way for one cell to go rouge and gobble up resources and make tons of copies to the detriment of the whole. Biology already puts tons of roadblocks in the way to this, and we can surely add more, but at the end of the day it’s such a huge incentive so things will go find the easier faster way to chemical equilibrium
- kiba 5y ago
  We probably won't kill cancer through one miracle cure, but probably through death by a thousand cuts. That and we probably need to repair the immune system. The incident of cancer increases with age, after all.
  - toomuchtodo 5y ago
    How do you improve the immune system to convey the improvements we’ve made with mRNA to it?
    - jcims 5y ago
      We haven't really made any improvements to the immune system with mRNA, we're just giving it some training film to be ready when the fight comes. An immune system that has a hair trigger to new antigens would likely cause more problems than it solves. Some kind of ability to have contagious antibodies might be an actual improvement but the fact that we don't see that in nature tells me it has downsides that are difficult to see.
      - deleted 5y ago
        [deleted]
      - KMag 5y ago
        > Some kind of ability to have contagious antibodies might be an actual improvement but the fact that we don't see that in nature tells me it has downsides that are difficult to see. My biology education is a bit weak, but off the top of my head, autoimmunity being contagious sounds like a likely side-effect of contagious antibodies.
    - tiborsaas 5y ago
      We could sample the actual cancer in the patient and custom print an mRNA cure to that specific person for maximum accuracy. The Pfizer/BioNTech vaccine was created in hours after Covid was sequenced. So this might not be a too far fetched idea.
      - DrAwdeOccarim 5y ago
        Easier said than done, but yes most mRNA companies are trying the non-personalized and personalized cancer vaccine idea. The issue is the immune system is held back, like a big bouncer holding you back in a fight. Checkpoint inhibitors remove that bouncer, but now you're drunk and throwing fists all over the place, hitting both your friends, the bouncer, and the hooligans at the same time...
  - cameronh90 5y ago
    I believe, as you hint towards, that the ultimate way to reduce cancer risk is to cure ageing. Most cancers are rare in your 20s and 30s, then get dramatically more common every year after from your mid 40s roughly. To me, this suggests that the mechanisms that stop you getting cancer (and your body/DNA repairing in general) are themselves failing. Of course, if everyone was 25 forever we'd still all eventually die of cancer, but it would take a lot longer than the current state of affairs.
  - vmception 5y ago
    The incidence of errors occurring and the incidence of error correction failing increases over time I think that has much less to do with the immune system, although I think that can be a factor too It’s just probability from a flawed replication process
  - DoreenMichele 5y ago
    Death by a thousand cuts is vastly saner than "Nuke it from orbit. It's the only way to be sure." when your body is the battlefield. But most people don't really want to hear that. We hear "big, scary death label disease" and we want someone to promise they can nuke it from orbit. No one wants to hear that we need to care for the body and foster its health while battling this "demon."
- tsimionescu 5y ago
  The interesting thing going against your fear is that there are organisms like blue whales that do not die of cancer, or at least for them it is an exceedingly rare disease. The reasons for this are not yet understood, and they may not be entirely applicable to humans (e.g. the sheer size of a blue whale may play an important role, since cancer would take much, much longer to grow to any noticeable proportion of the whale than in a human-sized organism), but at least it proves it's not completely impossible to have life without cancer.
  - pfdietz 5y ago
    Elephants have 20 copies of the TP53 tumor suppressor gene. https://www.nature.com/articles/nature.2015.18534 https://www.nature.com/articles/nature.2015.18534
    - wetpaws 5y ago
      Every time I read about it I'm baffled we are not doing the same for humans with gene editing.
      - pfdietz 5y ago
        I'm sure there are many side effects that could only be found and fixed on a mountain of dead babies. For example, if I understand correctly, this makes elephants very susceptible to radiation sickness, as their cells are on a hair trigger to destroy themselves at any sign of genetic damage.
  - space_fountain 5y ago
    I can't actually find a good source for blue whales not dying of cancer. I do see lots of sources claiming the rates are way lower than in humans, and that is indeed interesting. It's evidence that we could do better at suppressing cancer, but I'm very convinced that cells that can evolve eventually deciding to go rouge isn't something that be precisely stopped. Just made less likely
- agumonkey 5y ago
  I can envision a moment where non invasive intervention and monitoring can be precise enough to stop being a threat. Other than that yeah, I think it's a naturally emergent biological phenomenon that cannot be removed.

space_fountain 5y ago

I’m not a biologist, but how I imagine it is that cancer is just evolution + entropy. We can obviously get a lot better at controlling it, but it will always be there because there’s always a way for one cell to go rouge and gobble up resources and make tons of copies to the detriment of the whole. Biology already puts tons of roadblocks in the way to this, and we can surely add more, but at the end of the day it’s such a huge incentive so things will go find the easier faster way to chemical equilibrium

kiba 5y ago
We probably won't kill cancer through one miracle cure, but probably through death by a thousand cuts. That and we probably need to repair the immune system. The incident of cancer increases with age, after all.
- toomuchtodo 5y ago
  How do you improve the immune system to convey the improvements we’ve made with mRNA to it?
  - jcims 5y ago
    We haven't really made any improvements to the immune system with mRNA, we're just giving it some training film to be ready when the fight comes. An immune system that has a hair trigger to new antigens would likely cause more problems than it solves. Some kind of ability to have contagious antibodies might be an actual improvement but the fact that we don't see that in nature tells me it has downsides that are difficult to see.
    - deleted 5y ago
      [deleted]
    - KMag 5y ago
      > Some kind of ability to have contagious antibodies might be an actual improvement but the fact that we don't see that in nature tells me it has downsides that are difficult to see. My biology education is a bit weak, but off the top of my head, autoimmunity being contagious sounds like a likely side-effect of contagious antibodies.
  - tiborsaas 5y ago
    We could sample the actual cancer in the patient and custom print an mRNA cure to that specific person for maximum accuracy. The Pfizer/BioNTech vaccine was created in hours after Covid was sequenced. So this might not be a too far fetched idea.
    - DrAwdeOccarim 5y ago
      Easier said than done, but yes most mRNA companies are trying the non-personalized and personalized cancer vaccine idea. The issue is the immune system is held back, like a big bouncer holding you back in a fight. Checkpoint inhibitors remove that bouncer, but now you're drunk and throwing fists all over the place, hitting both your friends, the bouncer, and the hooligans at the same time...
- cameronh90 5y ago
  I believe, as you hint towards, that the ultimate way to reduce cancer risk is to cure ageing. Most cancers are rare in your 20s and 30s, then get dramatically more common every year after from your mid 40s roughly. To me, this suggests that the mechanisms that stop you getting cancer (and your body/DNA repairing in general) are themselves failing. Of course, if everyone was 25 forever we'd still all eventually die of cancer, but it would take a lot longer than the current state of affairs.
- vmception 5y ago
  The incidence of errors occurring and the incidence of error correction failing increases over time I think that has much less to do with the immune system, although I think that can be a factor too It’s just probability from a flawed replication process
- DoreenMichele 5y ago
  Death by a thousand cuts is vastly saner than "Nuke it from orbit. It's the only way to be sure." when your body is the battlefield. But most people don't really want to hear that. We hear "big, scary death label disease" and we want someone to promise they can nuke it from orbit. No one wants to hear that we need to care for the body and foster its health while battling this "demon."
tsimionescu 5y ago
The interesting thing going against your fear is that there are organisms like blue whales that do not die of cancer, or at least for them it is an exceedingly rare disease. The reasons for this are not yet understood, and they may not be entirely applicable to humans (e.g. the sheer size of a blue whale may play an important role, since cancer would take much, much longer to grow to any noticeable proportion of the whale than in a human-sized organism), but at least it proves it's not completely impossible to have life without cancer.
- pfdietz 5y ago
  Elephants have 20 copies of the TP53 tumor suppressor gene. https://www.nature.com/articles/nature.2015.18534 https://www.nature.com/articles/nature.2015.18534
  - wetpaws 5y ago
    Every time I read about it I'm baffled we are not doing the same for humans with gene editing.
    - pfdietz 5y ago
      I'm sure there are many side effects that could only be found and fixed on a mountain of dead babies. For example, if I understand correctly, this makes elephants very susceptible to radiation sickness, as their cells are on a hair trigger to destroy themselves at any sign of genetic damage.
- space_fountain 5y ago
  I can't actually find a good source for blue whales not dying of cancer. I do see lots of sources claiming the rates are way lower than in humans, and that is indeed interesting. It's evidence that we could do better at suppressing cancer, but I'm very convinced that cells that can evolve eventually deciding to go rouge isn't something that be precisely stopped. Just made less likely
agumonkey 5y ago
I can envision a moment where non invasive intervention and monitoring can be precise enough to stop being a threat. Other than that yeah, I think it's a naturally emergent biological phenomenon that cannot be removed.