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Comment by danieltillett | Hacker News Reader

>”...because we can cure cancer in mice.”

Actually as far as I know we can’t cure mice of cancer - by cancer I mean natural cancers that mice get as they age just like human cancers. I have looked through the literature in great detail and I can’t find a single recent paper where anyone has even tried curing mice of cancer. If anyone know of one I would love to read it.

The way we go about trying to cure cancer is insane. We basically take inbred mice, inject them with a cancer cell line to give them cancer, and then treat them with experimental drug X. This process is nothing like how real human cancers arise. On top of this we only test new drugs in people that have failed all other treatments and have very high tumour burdens. We then demand that the new drug have a significant effect in these patients despite us needing drugs that work in newly diagnosed patients. If we get a drug that works it is more by chance than design.

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>"I have looked through the literature in great detail and I can’t find a single recent paper where anyone has even tried curing mice of cancer."

It's interesting how your perspective will change after reading the literature. It is the same thing with the various mutations claimed to cause cancer. For example, in this thread someone claims mutations to BRAF cause cancer. I am nearly certain that inspecting the literature will not result in any studies where that gene in a normal cell was mutated, and then it took on the properties of a cancer cell.

Maybe we will see some data on many cell generations later and in conjunction with various other treatments, but not the direct experiment of "non-cancer cell + BRAF mutation = cancer cell" while "non-cancer ell + control treatment = non-cancer cell".

Cancer in humans is never driven by one mutation - if it were there is no way we could reach adulthood. Cancer is the slow process of accumulating mutations in cell lineages - the time between the first mutation in say BRAF and a metastatic cancer is 20 to 40 years. Lots of other mutations have to happen before you get clinical cancer.

>"the time between the first mutation in say BRAF and a metastatic cancer is 20 to 40 years"

Actually do you have a ref for this? I can't easily think of how they would date the mutation.

I haven’t got one off the top of my head, but it is pretty well known. An really good example was the atomic bombs in Japan. They tracked all the survivors and when they got cancer and the delay was in decades.

So which combinations of mutations cause cancer then? Replace BRAF in my pseudo-equations above with "combination of mutations".

There are hundreds of thousands of mutation combinations that lead to cancer. This is why it is such a difficult problem.

Has anyone done a proof of principle though. You only need to test one of the combinations. I don't think anyone has been able to do this.

This is a good question for which I don’t have the answer. We know from epidemiological research that you need at least 5 independent mutations to get to metastatic cancer. With the new CRISPR technology it should now be possible to make cells containing just 5 mutations which should then be able to be studied.

The bigger problem is these 5 mutations can be drawn from hundreds of possible genes so the combinations are almost endless.

>"We know from epidemiological research that you need at least 5 independent mutations to get to metastatic cancer."

This is all based on the Armitage and Doll 1954 theory, they write: "This result will be valid for large values of t (of the order of a human lifetime) provided that p_l x t, P_2 x t, ..., p_r x t are all sufficiently small (as could be assumed in an application of this theory to human cancer)" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2007940/

Here, the "the probability of occurrence of the r-th change, in that line of descent, is p, per unit time [t]". So obviously if p or t is large enough, the probability of dying from cancer goes above 1, which is non-physical. There is a simplification being made here that was reasonable in the pre-computer age. What happens if you implement the same theory without that simplification?

You're right, of course. BRAF mutations alone don't cause cancer. They're caused by the accumulation of key mutations coupled with clonal expansion. I oversimplified a bit while making a point about basket trials.

That's not what I meant. I said "and in conjunction with various other treatments", which was perhaps poor wording since by treatment I meant causing other mutations/etc. To my knowledge, no one has ever been able to take a normal cell, do X to it (where X is usually some combination of mutations), and see it becomes a cancer cell.

So we mostly use mice as soil to cure remission of already existing cancerous cells/tissue ? Not that similar to understanding cancer, at least cancer onset... Odd.

It is even worse than this as by controlling the number of cells injected you can make it very easy to cure the cancer.

The reason why this is done is it is much easier to do than the experiments that should be done. It is like the old joke about the drunk looking for his keys under the street light because the light is better despite have lost them in dark alley behind.

I hope organ generation/printing will help avoid these tricks. Isn't it the most promising way to make real progress ?

The most promising way would be to stop funding research if it is not done correctly and stop allowing people to publish papers with “play” research. No more use of inbred mice lines, more more injecting known cancers (only use natural cancers), no more testing of treatments that have no chance of working in humans.

The best suggestion I have seen is to make better use of all the millions of pets we have. Dogs and cats get cancer that is very similar to human cancer (much more so than mice) and these are all natural cancers. We need to encourage people to sign up their pets for cancer treatment and conduct many more trials in pets. The fact that we don’t do this at any scale is a sign that we are not too serious about curing cancer.

Involving people to treat their pet with current medicine looks like borderline impossible. If people think their dog will suffer they will skip that.

And research funding is probably conservative, since mice is the 'less bad' idea, money flow this way. Some competition may help changing habits.

There pet is already suffering - it has cancer after all. The alternative in most cases is to put the dog down.

More importantly this question has already been asked by researchers and most people are happy for their pets to participate in such trials especially when they know they are really helping cure cancer.

Aight then, my folk-understanding was off. Hoping it will help making steps.

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