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.

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

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.

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.

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."

How do you improve the immune system to convey the improvements we’ve made with mRNA to it?

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.

> 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.

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.

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...

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

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.

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

Elephants have 20 copies of the TP53 tumor suppressor gene.

https://www.nature.com/articles/nature.2015.18534

Every time I read about it I'm baffled we are not doing the same for humans with gene editing.

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.

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.

There is no sentience. It’s a trillion monkeys banging at a trillion typewriters.

If anything treating cancer is more akin to antibiotic resistance. One therapy usually just selects for the cancer that is resistant, so you relapse.

And cancer cells have notoriously fragile genomes. I remember reading a paper that sequence 1,000 breast cancer samples. There were about 800 different mutations that led to the cancer. Very little similarity between patients.

> There is no sentience. It’s a trillion monkeys banging at a trillion typewriters.

I get it but the human genome has ~4^3,200,000,000 possible combinations. Even single genes have 4^1000 possible combinations...that's a number with 600 zeroes in it. That's a trillion^50. It's just odd that the mutations always seem to zero in on the right spot pretty damn quickly.

It's a wonder we don't all have cancer. Our large functioning multi cellular bodies are a marvel.

Evidence suggest humans “get” cancer way more frequently than we’d expect. Cells are programmed to “self-destruct” if things go wrong and our immune system is primed to destroy cells that express certain proteins associated with uncontrolled growth.

It’s really the edge cases that get through.

I am curious if you have read, and of what you think of Jason Fung's book Cancer Code. Is it a fair overview of the papers you have read? What level of understanding does he achieve?

Survivalist? You do realize once the loved one dies,the cells have to die too. A bit counter-inituitive..

It is a tragedy of the commons scenario. The individual actors have no conscience or plan, of course, but it all amounts to the same: some cells can morph into freeloaders and those that morph into the most aggressive replicators "win" in the short term.

Unless perhaps if the cancer is transmissible.

Yes, quite. Sometimes it's too successful and outstrips its resource. Sounds familiar.

If you have a word you prefer I invite you to use it in the future.

I have been using "cancer", but "carcinoma" and "tumor" are common.

Those terms are not interchangeable.

Some cells survive the death of their organism. Like the HeLa line of cells. There's an interesting and tragic story behinds it too...

That’s because cancer only happens when it manages to survive or bypass every process in the human body that would normally prevent it.

It’s the pinnacle of (natural) selection bias.

I also had that moment where you're somehow in awe about all the reinforcing intricacies that allow cancer to persist. It's an odd form of anti-life.