The curious DNA circles that make treating cancer so hard
cen.acs.org
cen.acs.org
* Scientists discovered a relationship between cancer and extrachromosomal DNA (ecDNA) in 1965, but considered ecDNAs rare and not worth investigating.
* Researchers subsequently learned that ecDNAs are 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...
The presence of telomerase prevents telomere shortening in cancer cells and gives the ability to divide an unlimited number of times in a laboratory cell culture plate.
But the aging process is not reversed, so a multicellular complex organism would eventually die.
Except, they seem to have that in yeast, which are distinguished by a need to reproduce fast like tumor cells. If they have been ignored all this time, maybe they are just a normal part of eukaryote biology?
In the nematode world, we create extrachromosomal arrays of transgenes by injecting plasmids into the worm’s gonad that then get passed down to progeny; the expression we see is almost always variable and mosaic and not every cell ends up showing it.
I would guess this technique used for decades in the field is actually an induced version of these!
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.
That and we probably need to repair the immune system. The incident of cancer increases with age, after all.
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.
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.
The Pfizer/BioNTech vaccine was created in hours after Covid was sequenced. So this might not be a too far fetched idea.
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.
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
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."
If you have a word you prefer I invite you to use it in the future.
It’s the pinnacle of (natural) selection bias.
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.
It’s really the edge cases that get through.
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.
equipment, material, and people costs are prohibitively high for now. hopefully one day.
But grant committees are controlled by the older members of each sub-field. They are biased toward what seemed important to them when they were young, but also against what experience has taught them tend to be dead ends. They want questions explored that have gone wanting for decades. Young researchers will eventually graduate to grant committees, and fund what they wish had been looked into decades before.
We can see systematic failure in, e.g., Alzheimer syndrome research, still funding suppression of amyloid plaques and tau tangles decades after every such avenue was found to fizzle. But we don't know a better way to organize evaluating grant applications. We would not know how to evaluate any change proposed. And, we don't know how to change committees over if we found a better one.
Each sub-field has its own dynamic, independent of all the others. Probably some have evolved a method that works well for their sub-field, for now, but would certainly be wrong for the next sub-field over, and will be wrong in its own in ten years. They are all playing catch-up all the time. The only thing that keeps it working at all is that they are run by smart people who have had to solve many different hard problems, and those people retire on a regular schedule.
science funding is indeed broken.
only 7% of NIH grants go to researchers under 40.
tesla, apple, and many impactful companies were started by founders under 40. watson, crick, and currie were all under 40 when making seminal contributions to science. imagine how many breakthrough ideas are gated in science right now.
the NIH is amazing but not allowed to take risk: how can we fund more unestablished scientists?
let's hope the day comes soon.
i've returned to issac asimov's response to innovation: find the smartest people, pay them a stipend contingent on completing some quick menial task, and then leave them be for a few weeks. out the other end you'll have innovations.
startups like https://mbcbiolabs.com are starting to lower lab costs, and this trend will only accelerate over time.
what are your favorite resources/labs for tracking research?
Some people have been working on combining two (or more) factors in order to only activate when in the right spot: https://www.science.org/content/blog-post/two-steps-activati...
My guess is that this is how the body actually works.
At the chemical level, the human body has many highly individually specific things (like enzymes and receptors).
However, at the system level, it's probably easier to take two slightly specific things and combine them to make something that is specific enough but not too brittle.