A New Mode of Cancer Treatment - https://news.ycombinator.com/item?id=36982813 - Aug 2023 (205 comments)
New targeted chemotherapy able to kill all solid tumors in preclinical research - https://news.ycombinator.com/item?id=36978199 - Aug 2023 (32 comments)
'Cancer-killing pill' is now being tested on humans - https://news.ycombinator.com/item?id=36969500 - Aug 2023 (33 comments)
Cancer pill AOH1996 shows promise in annihilating all solid tumours - https://news.ycombinator.com/item?id=36960895 - Aug 2023 (19 comments)
Cancer pill AOH1996 shows promise in annihilating all solid tumours - https://news.ycombinator.com/item?id=36960292 - Aug 2023 (16 comments)
Edit: @dang: Thanks, incorporated your addition.
Look at that molecular structure. Incredible.
Two amide bonds, a completely unremarkable aryl ether and an unsubstituted naphthalene ring system. No fussy weird metals or bonds that need pampering, no chiral carbon atom in sight.
You could probably pay someone a very modest amount of money to end up with kilograms of this stuff, and it would probably not degrade at all under ambient conditions.
I wouldn't be surprised if we soon see desperate, sick, rich people try this out on themselves, skipping FDA approval.
Beautiful, uplifting news. Let's hope the clinical trials proceed without issue.
Something about this delivery reminds of the business-card scene from Psycho [0].
> Look at that subtle off-white coloring, the tasteful thickness of it--Oh my God, it even has a watermark..."
I first thought it was a joke because of the two "HN" bonds hah, pardon me.
We all should hope that it has high specificity for the mutant PCNA, and doesn't affect healthy cells... clinical trials will investigate this.
[0] https://en.m.wikipedia.org/wiki/Proliferating_cell_nuclear_a...
The drug developers noticed that (a class of) cancer cells involve a shape change in the molecule that clamps on to DNA strands for the purposes of replication and repair. The molecule targets that shape change and thus prevents (a class of) cancer cells from being able to maintain and replicate their DNA.
Cancel cells die and can't replicate = no cancer.
"AOH1996 is a very unremarkable-looking molecule - to be honest, it looks like the sort of stuff that you used to see in old combinatorial chemistry libraries in the late 90s and early 2000s, a couple of aryl-rich groups strung together with amide bonds."
https://www.science.org/content/blog-post/new-mode-cancer-tr...
“I hope that human cancers will prove vulnerable to this new mode of attack in the clinic, and that they are not able to mutate around it with new forms of caPCNA too quickly, either.”
Even if this does prove effective in humans, eventually cancer cell defenses will evolve to get around it.
I much prefer your description of the molecule than the one found on its Wikipedia page.
I know nothing about the FDA but for things like terminal cancer treatment, shouldn't there be a blanket exemption for "if the patient so wish, they can take whatever drugs they want even if unapproved"? When facing certain death, what's the worst that can happen? You die a bit sooner?
The second way is that drugs/devices are considered against their intended use. So the argument for using more dangerous things is much easier if you are treating brain tumors than common colds. There even are fast-track (e.g. mRNA vaccine for covid) but won't be pulled out for niche uses.
What this doesn't cover is things produced in uncontrolled ways, or "i read this on the internet and want a prescription". I can see how this is frustrating for people who are willing to try anything, but I can also see the liability side.
> "When facing certain death, what's the worst that can happen? You die a bit sooner?"
Part of the problem is you certainly can make things worse, and you can make them systemically more expensive. It's one thing to say "I'm dying anyway and I want to try this" but quite another to add "and if it goes badly I expect you to try and deal with it". No easy answers, really.
Having cancer already sucks enough, having businesses and whatnot vulturing over your condition to sell you shit that doesn't work wouldn't really make it better?
But, if we know which cells to target and what their structure is, can’t we just extract some healthy cells, reproduce them, kill all cells which would dock to that pill, insert reproduced healthy cells?
So with that we don’t have to care if it attacks healthy cells, or is that reproduction idea not possible?
https://chat.openai.com/share/28d9b203-1cb5-405b-a109-0f5042...
Basically I wanted to see if your comment, along with the detailed description of the molecular structure, could lead the AI to guess how the compound could be useful. I then proceeded to drop more and more hints and asked it to use those hints along with the structure to guess at a potential mechanism of action. In any case, it certainly helped explain to me what you were talking about!
From the article in Cell:
"Given orally, AOH1996 suppresses tumor growth but causes no discernable side effect" is a VERY different result.
You stop the cancer cell reproduction and overall tumor growth, you also kill the cancer.
the growth rate could be suppressed to match the attrition rate and turn into a steady state, rather than eradication of the mutant cell lines (and their progeny).
https://www.science.org/content/blog-post/new-mode-cancer-tr...
Named after a girl that died. Resulted in fundraising for Neuroblastoma, and this medicine.
A working treatment for many cancers will bump many more preventable forms of deaths up the charts - obesity, cars, weapons. I hope that people will be inspired to take more significant actions to reduce those when we've tackled these really really hard ones.
And due to the potential low-cost, easy administration, and storage requirements, I am reminded a bit of how antibiotics ended up working in developing countries. Doctors prescribe them for every pain, making them ineffective at best and spawning antibiotic-resistant bugs at worst. I hope the researchers are able to consider this angle (overprescription) before these medicines become a widely distributed thing in other parts of the world.
It's an exciting decade for medicine. I hope that if we don't see the efficacy we want with this one, that more "simple" formulations will come around that do work.
Or read Derek Lowe's response on AOH1996:
https://www.science.org/content/blog-post/new-mode-cancer-tr...
Or read about the drug that came before it, but didn't metabolize well:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279569/
Or read about other new, interesting anti-cancer drugs:
https://med.stanford.edu/cancer/about/news/rewiring-cancer-c...
We need some good news these days.
This is the actual article:
https://www.cell.com/cell-chemical-biology/pdfExtended/S2451...
I recommend replacing the link and the title with what appears on the Cell website.
>100% of solid tumors
Solid tumors == all cancer, or would something like a lymph node cancer not be included?
Conspiracy idea: such a simple drug is not what Big Pharma wants, thus was never investigated.
Hopefully, if effective, it's affordable for people worldwide.
Arsenic also kills 100% of tumors in vitro.
In vitro doesn't answers the question of "can this drug be taken safely" nor "can this drug be delivered to the cancer cells"
I mean, the track record of such drugs still suggests it'll likely not live up to the hype of the title here, but that's the point of further research, which does appear to be happening. It's quite likely there's some unforeseen limitation, but hey, we can always hope.
Phase 2: does it appear to work as intended, tested in a larger number of people
Phase 3: is it better than alternatives.
Then approval, followed by monitoring of the drug and side effects.
There's also an additional phase of getting insurance to pay for the new drug, which can be the most difficult.
https://www.cancer.org/cancer/managing-cancer/making-treatme...
Phase 1 is pretty big on safety: sentinel dosing, then gradually increasing doses until the established max is reached or until serious side effects show up. Generally also includes PK/PD aspects: what is the half-life, how long it’s detectable in the body, does this match the modeling? How is the drug eliminated? All this is used to refine the dosing (if need be) but also provides a lot of the information needed for the safety documentation.
It seems strange to me that we can't give such an important novel drug the same treatment. The population size is smaller than global and the effect would be huge. I would seriously doubt anyone stricken with cancer would hesitate to agree to the same "experimental treatment" paperwork we all got when we were vaccinated.
We have MOUNTAINS of things that stop cancer in mice and sometimes other animals, that don't or won't pan out.
The superconducting results are much closer to if this paper was a small scale human study. Then you would likely see the same kind of "open all the floodgates" ramp up of effort.
Bunch more discussion over here: https://news.ycombinator.com/item?id=36982813
One of a number of posts over last few days
All it might take is some instagram cancer influencers, a lab in india or china and some darkweb transactions to DIY your cancer away... if this is so incredibly effective and safe in humans, too.
Or DIY yourself away accidentally. But I guess that would make it a tie, since the cancer dies as well...
Thalidomide used to cost $6 per capsule in the '70s when it was given for morning sickness (yes, I know, birth defects) but as soon as they found out it cured cancer the price went up to $18,000 and that's on GoodRx lol. [1] Harvoni for Hep C is $94,500 for a 12-week course.
Drugs aren't priced based on the cost to manufacture but based on the projected savings as compared to existing treatments for the medical system - or based on the value the provide to customers. Curing cancer provides value -> price moons.
Unfortunately healthcare is not and cannot by definition be a free market as a free market requires the voluntary exchange of money for goods and services. "Pay me or die of cancer" is not a voluntary exchange but a coerced one - hence the failure of pricing and availability of necessary care you see in the US.
I see it as mockery of some maladjusted status-obsessed men as they fawn and suffer over trivial differences in pretty-much-identical plain white business cards. Every card says the same thing except for the name, and many of the things being described aren't even true. (For example, not embossed, no watermark, etc.)
Cancer becomes tolerant to drugs separately for each patient. I.e. initially it isn't resistant, but the drug used on a patient puts evolutionary pressure on the cancer to work around the drug. What this means is that people have more months or years to live, which is great. (I am not a doctor).
The ABVD regime starts with the same baseline on all hodgkin's lymphoma patients, and 'cures' cancer permanently in quite a large number of them.
Instead, this would target both healthy and cancerous cells. However, the idea is that the cancer cells are more susceptible to the drug. Healthy cells will be affected, but cancer cells will be affected more, and are more unstable, so losing PCNA will have more of an effect on the cancer cells.
The main idea is to do as much damage to the cancer cells while doing as little to normal cells as possible.
Edit: after reading the paper, the drug is targeting a cancer specific isoform of PCNA. This isn’t a mutation, but a slightly different form of the existing protein. Cancers tend to rely on this specific version, while healthy cells can use a different isoform (or both?). A selective inhibitor for this isoform would be cancer cell specific. There would still be some effect on healthy cells, but not as much as with a traditional cytotoxic chemotherapy.
I wonder how something like that comes about? Is there something special about that isoform that is necessary for tumor growth or what?
Edit: exactly -> "It was created to target a specific variant of PCNA found only in cancer cells. This protein is crucial in the body for DNA repair, but targeting it was difficult because of its role in healthy cells. By going after only the variant, it may be possible to selectively target only cancer cells"
From Wikipedia
It is targeting a mutated version.
https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...
The coding sequence for an isoform is part of the normal gene DNA sequence, but the cells can “choose” which version to make. In this case the caPCNA isoform is the form predominantly expressed in cancer cells.
(There is a mechanism where novel splicing isoforms can be produced by a mutation, but this doesn’t seem to be one of those.)