[HN Gopher] The curious DNA circles that make treating cancer so...
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The curious DNA circles that make treating cancer so hard
Author : panabee
Score : 40 points
Date : 2021-10-02 19:26 UTC (3 hours ago)
(HTM) web link (cen.acs.org)
(TXT) w3m dump (cen.acs.org)
| amelius wrote:
| Can't we develop some protein that locks onto these circles and
| then triggers cell death?
| monkeycantype wrote:
| or more likely find an organism that already has.
| thaumasiotes wrote:
| Wouldn't that protein need to penetrate the cell wall? You'd
| need something more like a virus.
| andrewflnr wrote:
| I expect the tricky part, or at least a tricky part, is
| distinguishing an ecDNA circle from healthy chromosomal DNA.
| More speculatively, bacterial DNA looks kind of similar, and
| you don't want to indiscriminately kill your gut bacteria.
| chasil wrote:
| The mitochondria also have circular DNA, exclusively. I
| wonder how similar these forms are.
| jcims wrote:
| I, like so many others, had a sudden motivation to develop my
| understanding of cancer.
|
| Once you've read your hundredth paper and followed as many
| clinical trials, it takes on another form. Near sentience, its
| the ultimate survivalist. It's too bad it has such a devastating
| outcome on loved ones, we'd all admire it otherwise.
| DrAwdeOccarim wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| How do you improve the immune system to convey the
| improvements we've made with mRNA to it?
| jcims wrote:
| 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]
| vorejdajo wrote:
| Survivalist? You do realize once the loved one dies,the cells
| have to die too. A bit counter-inituitive..
| tasty_freeze wrote:
| 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.
| [deleted]
| jcims wrote:
| 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.
| DrAwdeOccarim wrote:
| Really fascinating! I wonder if these cells all have defects in
| innate immune sensing of cytosolic DNA. Like, do cGAS/MAPK/etc.
| require linear for recognition like RIG-I does for dsRNA or are
| they all mutated/shutdown in these cells. Would be interesting to
| see the innate immune transcriptome with and without ecDNA.
| andrea81 wrote:
| Which type of cancer?
| panabee wrote:
| Key Points:
|
| * Scientists discovered a relationship between cancer and
| extrachromosomal DNA (ecDNA) in 1965, but considered ecDNAs rare
| and not worth investigating.
|
| * Researchers subsequently learned that ecDNA is common and
| central to the behavior of some of the most aggressive forms of
| cancer, enabling remarkably elevated levels of oncogene
| transcription, creating new gene regulatory interactions, and
| providing a powerful mechanism for rapid change that can drive
| very high oncogene copy numbers or allow cancer cells to resist
| treatment.
|
| * Like Ptolemy's flawed map that placed Earth at the center of
| the solar system, cancer researchers today may be analyzing genes
| and diseases with flawed maps.
|
| Related Articles
|
| * https://www.the-scientist.com/features/cancer-may-be-driven-...
|
| * https://chemh.stanford.edu/news/shining-light-extrachromosom...
| jcims wrote:
| Would be interesting to see if the mechanisms underlying
| cancer's genetic agility could ultimately be put to use to
| search for solutions to other problems.
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