Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Cancer therapy by RNA delivery to dendritic cells

nature.com

Post reply on HN
Print view View original

31–40 of 44 posts

Re: Cancer therapy by RNA delivery to dendritic cells

#31

Post by rcthompson »

pvnick wrote: post #29
rcthompson wrote: post #24

This is certainly an interesting and theoretically promising method, that, if it works, should make it fairly easy to develop specific personalized "vaccines" for each person's cancer. For background, dendritic cells are a type of antigen-presenting cells, which means their job is to pick up proteins, break them up into small pieces (antigens), and then show those pieces to T-cells, whereupon the T-cells can either s…

Great summary, thanks for that. This therapy appears fairly elegant. Let's hope it makes it through trials.

Yes, it certainly seems elegant, but with biology (and science in general), you always have to keep in mind that the (apparent) elegance of an approach is predicated on the assumption that we have an accurate understanding of how the system in question works, which frequently turns out not to be the case.

Re: Cancer therapy by RNA delivery to dendritic cells

#32

Post by rcthompson »

nibs wrote: post #28
rcthompson wrote: post #25

Earlier quoted context omitted.

Assuming this kind of therapy is effective in humans, the rate-limiting step is identifying a protein in the cancer that is either not produced in normal cells or sufficiently mutated relative to the same protein in normal cells, such that the immune system targeting that protein will only kill cancer cells. Otherwise you'd just induce autoimmune disease.

This was my first thought when I read it. How do you aim it(?).

Are you asking how to identify such a target protein? Well, you could sequence cancer peptides using mass spectrometry, or sequence the cancer cells' genome, and look for proteins that are sufficiently mutated relative to the wild type copy. However, we already have pretty good knowledge of which genes tend to be mutated most often in cancer cells, so you could do targeted sequencing on those genes first to look for low-hanging fruit. In general, it's still a hard problem, though.

Re: Cancer therapy by RNA delivery to dendritic cells

#33

Post by rcthompson »

baldfat wrote: post #10
Aelinsaar wrote: post #8

Earlier quoted context omitted.

It's very exciting, but as these therapies become more successful, we're going to have to tackle the adverse reactions both acute, and chronic. Granted, you're surviving cancer so that's not the primary concern, but it will be a concern.

Well that is the Number One Reason why they are going immuntheraphy the side effects are minor compared to Chemo and Radiation. This is your own body fighting the cancer.

There's nothing to say that leveraging your own immune system will necessarily reduce the frequency or severity of side effects relative to current therapies. Your immune system is quite capable of killing just about any cell in your body, foreign or not. The multitude of different autoimmune diseases are clear evidence of that fact.

Re: Cancer therapy by RNA delivery to dendritic cells

#34

Post by danieltillett »

pessimist wrote: post #11

To keep things in perspective, in oncology the current success rate of treatments that enter trials is just 5%! See http://blogs.sciencemag.org/pipeline/archives/2016/06/02/are... . Immunotherapy is indeed the most promising approach to cancer therapy so I'm optimistic, but the odds of success here are 1-in-20 if this is an average study, or perhaps 1-in-5 at best.

You certainly have chosen the right user name, but it is a logical error to use the success rate of all cancer trials to calculate the chance of success of this immunotherapy trial.

Re: Cancer therapy by RNA delivery to dendritic cells

#35

Post by rcthompson »

dekhn wrote: post #27
Houshalter wrote: post #18

Earlier quoted context omitted.

Because evolution doesn't work on a species level, it works on a gene level. Genes that help propagate themselves spread more. A cancer causing gene would almost certainly be selected against, vs a gene that caused you to live longer and have more children - and spread more copies of itself. The reason people die is not because it's better for evolution. It's because evolution simply doesn't care about maximizing lif…

I take issue with your first statement- evolution certainly works at the species level (in the sense that population genetics is a thing). It does appear there is a population fitness that is selected for when two desirable phenotypes can't be accomodated in a single individual. Also, "Most organisms die long before they get cancer, so the fitness of a gene that prevents cancer is pretty small." ignores the fact that…

The term "tumor suppressor" doesn't necessarily mean that the gene exists for the sole purpose of preventing cancer. It just means that the protein's normal function happens to prevent cells from becoming cancerous. Many DNA-repair proteins fall into this category, for example, simply because repairing errors in a cell's DNA reduces the probability of that cell accumulating cancer-causing mutations. And yet, DNA-repair proteins pre-date the evolution of multicellular organisms, so they cannot possibly have evolved as a response to cancer.

In practice, the term "tumor suppressor" generally means a gene for which recessive loss of function mutations are associated with cancer (i.e. you have to lose function of both copies of the gene in the same cell before there's an effect), while "oncogene" means a gene for which dominant gain of function mutations are associated with cancer (i.e. mutation in one copy of the gene is sufficient to have an effect). Neither term implies anything about how the gene evolved or whether selection due to cancer was a factor in the evolution of the gene.

Re: Cancer therapy by RNA delivery to dendritic cells

#36

Post by rcthompson »

wyldfire wrote: post #13

Stupid/insensitive question: what if cancer were a species "feature" earned through evolution that helps reap people who made it through their reproductive years without accident or disease but are now more hindrance than help to the species?

The fact that every cancer is different and arises due to the accumulation of random mutations is strong evidence that it is the result of dysregulation, not a regulated process. If it was adaptive to have an age-limiting "kill switch", there are much more direct ways to achieve that. (e.g.: https://en.wikipedia.org/wiki/Bamboo#Mass_flowering)

Re: Cancer therapy by RNA delivery to dendritic cells

#37

Post by rcthompson »

untilHellbanned wrote: post #21
Houshalter wrote: post #18

Earlier quoted context omitted.

Because evolution doesn't work on a species level, it works on a gene level. Genes that help propagate themselves spread more. A cancer causing gene would almost certainly be selected against, vs a gene that caused you to live longer and have more children - and spread more copies of itself. The reason people die is not because it's better for evolution. It's because evolution simply doesn't care about maximizing lif…

I think you are arguing on two different levels. I'm a professor biologist and though it strikes me as a pretty indirect mechanism (arguing the effect size could be small), I see some merit to the commenter's idea.

The current hypothesis is that humans have a longer lifespan because having living grandparents conferred a survival advantage over having only parents. Arguing that elderly relatives confer a disadvantage would seem to directly contradict that hypothesis, unless somehow grandparents were beneficial but great grandparents were not.

Re: Cancer therapy by RNA delivery to dendritic cells

#38

Post by muditjai »

rcthompson wrote: post #31
pvnick wrote: post #29

Earlier quoted context omitted.

Great summary, thanks for that. This therapy appears fairly elegant. Let's hope it makes it through trials.

Yes, it certainly seems elegant, but with biology (and science in general), you always have to keep in mind that the (apparent) elegance of an approach is predicated on the assumption that we have an accurate understanding of how the system in question works, which frequently turns out not to be the case.

Thanks for the great summary. But I'm guessing previous immunotherapy based treatments are also based on stimulating T-cells to fight cancer cells. Any idea why they didn't work? This method only makes it easy to stimulate T-cells, but what about mutations in cancer.

Re: Cancer therapy by RNA delivery to dendritic cells

#39

Post by dekhn »

rcthompson wrote: post #35
dekhn wrote: post #27

Earlier quoted context omitted.

I take issue with your first statement- evolution certainly works at the species level (in the sense that population genetics is a thing). It does appear there is a population fitness that is selected for when two desirable phenotypes can't be accomodated in a single individual. Also, "Most organisms die long before they get cancer, so the fitness of a gene that prevents cancer is pretty small." ignores the fact that…

The term "tumor suppressor" doesn't necessarily mean that the gene exists for the sole purpose of preventing cancer. It just means that the protein's normal function happens to prevent cells from becoming cancerous. Many DNA-repair proteins fall into this category, for example, simply because repairing errors in a cell's DNA reduces the probability of that cell accumulating cancer-causing mutations. And yet, DNA-repa…

While most of what you say is generally consistent with mainstream science (including my copy of Cancer by Weinberg, AKA, "the bible"), it neither refutes my point, nor provides any support for the parent poster's claim.

Also, "DNA-repair proteins pre-date the evolution of multicellular organisms, so they cannot possibly have evolved as a response to cancer." is not a valid argument. There are eukaryotic DNA repair proteins not found in bacteria, for which evolutionary evidence shows they evolved more recently. A number of such genes aren't just DNA repair, but cell cycle controllers that respond to DNA damage and coordinate complex activity. Whether they are "sole purpose of preventing cancer", is a very deep question, and goes to the heart of the nature of cancer. For example, naked mole rats either never or very rarely get cancer; current thinking is that hyaluronase they produce has a protective effect. Did the genes that make enzymes that produce hyaluronase evolve "specifically to prevent cancer", or did they play other roles and just incidentally provide cancer protection? Those are challenging hypotheses to express and prove either way.

I'm sure you're familiar with the Hallmarks of Cancer.

Re: Cancer therapy by RNA delivery to dendritic cells

#40

Post by Houshalter »

dekhn wrote: post #27
Houshalter wrote: post #18

Earlier quoted context omitted.

Because evolution doesn't work on a species level, it works on a gene level. Genes that help propagate themselves spread more. A cancer causing gene would almost certainly be selected against, vs a gene that caused you to live longer and have more children - and spread more copies of itself. The reason people die is not because it's better for evolution. It's because evolution simply doesn't care about maximizing lif…

I take issue with your first statement- evolution certainly works at the species level (in the sense that population genetics is a thing). It does appear there is a population fitness that is selected for when two desirable phenotypes can't be accomodated in a single individual. Also, "Most organisms die long before they get cancer, so the fitness of a gene that prevents cancer is pretty small." ignores the fact that…

>evolution certainly works at the species level (in the sense that population genetics is a thing).

That's not at the species level. That's, at the very best, at the level of a very small group. And most of those theories have generally been discredited - it only works if the beneficial effect on the group is sufficiently large, see http://lesswrong.com/lw/kw/the_tragedy_of_group_selectionism...

>there are genes preventing cancer (tumor suppressors), and those genes are under active selection.

That doesn't contradict what I said. Those genes work well enough to prevent cancer in young organisms, but they are clearly not enough to stop all cancer.

Why hasn't evolution evolved away all cancer? Because even if there was a gene that could decrease cancer risk by an additional 1%, it wouldn't actually increase fitness that much. A 1% decrease in risk is small on it's own, and then it only affects the 1% of organisms that haven't already died of other things. Preventing cancer is just not in evolution's priorities - at least not past a certain point.

Post reply on HN