Cancer therapy by RNA delivery to dendritic cells • Hacker News Board

Re: Cancer therapy by RNA delivery to dendritic cells

#41

Post by dekhn » Thu, Jun 02, 2016, 11:46 PM UTC

Houshalter wrote: post #40

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…

>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 prev…

I concede I was probably inaccurate in my statement about evolution and the species level; note, however, that I disagree with people who believe that the gene is the unit of evolutionary selection (I would refine it to say "functional region" rather than gene because I believe that mutations in enhancers and other transcriptional activators play a bigger role in evolution that mainstream science).

On to your second reply: I basically agree. We're mostly arguing about where that certain point is. Problem is: cancer is a disease that is closely tied to many necessary functional parts of multicellular organisms.

In a sense cancer is what gets people who weren't got by something more acute earlier, and probably evolution is addressing the more acute issues with a higher priority.

Re: Cancer therapy by RNA delivery to dendritic cells

#42

Post by rcthompson » Fri, Jun 03, 2016, 12:23 AM UTC

muditjai wrote: post #38

rcthompson wrote: post #31

Earlier quoted context omitted.

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.

The job of the immune system is to distinguish self from non-self and to seek and destroy any non-self that it discovers. If you want to get the immune system to fight something, you need to get it to recognize that something as non-self, preferably without also forcing it to recognize your own healthy cells as non-self (because then you'd have autoimmune disease). Cancer is an especially difficult case for the immune system because for the most part, cancer cells are your own cells with just a few mutations[1]. The vast majority of proteins produced by cancer cells are the same proteins that your healthy cells produce. They may be produced in different proportions, regulated differently, etc., but they are the same proteins. Even the proteins that mutated could have only a single amino acid change relative to the original. So the difference between healthy cells and cancer cells at a molecular level is much more subtle than the difference between your cells and bacterial cells, for example. It's not impossible for your immune system to identify cancer cells, but it's obviously not guaranteed either. (There's a nigh-untestable theory that a majority of cancers are actually detected and destroyed by the immune system long before they become symptomatic, so the ones we see are just the ones that managed to evade the immune system in their early stages.)

As I've mentioned above, this paper skips the hard part of finding a suitable protein target by picking two proof-of-concept cancer models for which a suitable "non-self" target is already known.

[1] Actually many mutations, but few that affect protein sequences, which are what T-cells mainly look at.

Re: Cancer therapy by RNA delivery to dendritic cells

#43

Post by untilHellbanned » Fri, Jun 03, 2016, 9:05 AM UTC

rcthompson wrote: post #37

untilHellbanned wrote: post #21

Earlier quoted context omitted.

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.

A current hypothesis. There is always room for more ideas.

Re: Cancer therapy by RNA delivery to dendritic cells

#44

Post by RosenJD4 » Fri, Jun 03, 2016, 11:16 PM UTC

gww wrote: post #15

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?

I would argue that cancer is more of a consequence of aging, genetics, and environmental factors and not a "feature". Cells have evolved multiple mechanisms to prevent rampant and uncontrolled growth. With cancer these mechanisms are perturbed through genetic alterations due to "bad luck" or the consequences I mentioned previously.

You can also think of cancer as a consequence of multicellularity.

Multicellular organisms need checks on how often and by how much a group of their cells can multiply. A liver must contain a specific amount of liver cells, and cancer occurs when these cells are able to continually divide and eventually activate non liver specific genes.

The cells of a multicellular organism become highly altruistic because each cell of the organism gives up its ability to reproduce in order to provide a chance for the organism's gametes to produce a new living organism.

So wyldfire's original comment on Cancer being a 'feature' is not necessarily incorrect, however the explanation is.

Cancer occurs when the contract that states that the Liver cells, who cannot reproduce, become able to continually divide without checks and balances. You can also almost think of Cancer as Cellular natural selection and evolution within the body. Cancer is a feature and consequence of multicellularity and likely not adaptive in any way such as sickle cell anemia and malaria resistance.

An awesome book which touches on this in addition to other history or cancer is The Emperor of all Maladies http://www.amazon.com/Emperor-All-Maladies-Biography-Cancer/...