New targeted chemotherapy able to kill all solid tumors in preclinical research(eurekalert.org)
eurekalert.org
New targeted chemotherapy able to kill all solid tumors in preclinical research
https://www.eurekalert.org/news-releases/997141
33 comments
Quite encouraging, hopefully will get some good results in the spring of 2024.
I wonder why the PR now: this phase I clinical trial started in 2021.
https://www.cancer.gov/about-cancer/treatment/clinical-trial...
OK, somebody please ruin my excitement now and tell me how this isn’t a miracle cancer cure.
It’s not. It’s just a molecule that binds to one mutation on one protein, albeit a very important one. There are many types of cancer that don't involve mutations of this particular protein.
That’s not a reason to lose hope, this is in fact a remarkable achievement. It’s part of a broader story in which humans are becoming more and more effective at building individual molecules that fit into precise grooves in proteins, changing their shape by distances measured in the width of a hydrogen atom.
I hope you can see how difficult this is. It’s the work of lifetimes now, but there is a constant march of improvement to the techniques for measuring protein binding, huge recent jumps in our understanding of protein folding (AlphaFold), and in our ability to synthesize molecules that bind to proteins. Most of that is the kind of technical work that doesn’t make headlines, but it compounds over time into discoveries like the one described in the article
That’s not a reason to lose hope, this is in fact a remarkable achievement. It’s part of a broader story in which humans are becoming more and more effective at building individual molecules that fit into precise grooves in proteins, changing their shape by distances measured in the width of a hydrogen atom.
I hope you can see how difficult this is. It’s the work of lifetimes now, but there is a constant march of improvement to the techniques for measuring protein binding, huge recent jumps in our understanding of protein folding (AlphaFold), and in our ability to synthesize molecules that bind to proteins. Most of that is the kind of technical work that doesn’t make headlines, but it compounds over time into discoveries like the one described in the article
Because cells, not just cancer, will find new ways to get around pathway blocks. Also, it's predecessor, AOH1160, didn't work:
https://pubmed.ncbi.nlm.nih.gov/29967249/
https://news.ucr.edu/articles/2019/10/02/research-focus-smal...
This is a single pathway block, systemic chemotherapy, but it does sound interesting. It binds to the PCNA region, and blocks it from assisting in repairing damaged DNA and keeps cells from replicating.
Chemotherapy does a good job, too, of stopping cell replication through a variety of methods. Yet cancer cells mutate and sometimes find away around it (called platinum resistance).
The beauty of AOH1996, is that it metabolizes well and seems (in animals, human clinical trials underway) to have low side effects. Seems to work in dogs? We'll have to see how humans cope with this.
Full article: https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...
https://pubmed.ncbi.nlm.nih.gov/29967249/
https://news.ucr.edu/articles/2019/10/02/research-focus-smal...
This is a single pathway block, systemic chemotherapy, but it does sound interesting. It binds to the PCNA region, and blocks it from assisting in repairing damaged DNA and keeps cells from replicating.
Chemotherapy does a good job, too, of stopping cell replication through a variety of methods. Yet cancer cells mutate and sometimes find away around it (called platinum resistance).
The beauty of AOH1996, is that it metabolizes well and seems (in animals, human clinical trials underway) to have low side effects. Seems to work in dogs? We'll have to see how humans cope with this.
Full article: https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...
Even if this perfect magical cure exists, it doesn't guarantee that we can witness or access it.
Dr. Carl June, leading a charity and publicly funded program, developed CAR T cell gene therapy, which successfully cured leukemia. However, it somehow ended up in the hands of Novartis. The cost of a single therapy was $20,000, but now it is being sold at price of $475,000, making it unaffordable for the majority of people. Have you ever heard about this?
https://www.technologyreview.com/2017/08/30/149399/the-fda-h...
https://landdestroyer.blogspot.com/2017/08/big-pharma-novart...
Dr. Carl June, leading a charity and publicly funded program, developed CAR T cell gene therapy, which successfully cured leukemia. However, it somehow ended up in the hands of Novartis. The cost of a single therapy was $20,000, but now it is being sold at price of $475,000, making it unaffordable for the majority of people. Have you ever heard about this?
https://www.technologyreview.com/2017/08/30/149399/the-fda-h...
https://landdestroyer.blogspot.com/2017/08/big-pharma-novart...
CAR T therapy is incredibly laborious.
https://www.dana-farber.org/cellular-therapies-program/car-t...
https://www.dana-farber.org/cellular-therapies-program/car-t...
> The cost of a single therapy was $20,000,
I mean, a single person who is not an accountant and sounds like they possibly have an axe to grind is not the most compelling source for how much the treatment really costs novatis to deliver.
I mean, a single person who is not an accountant and sounds like they possibly have an axe to grind is not the most compelling source for how much the treatment really costs novatis to deliver.
Well this is despicable...
It’s also completely untrue. In reality the high cost is not because of greed but because of high manufacturing cost and the necessity for long hospital follow-up. Novartis is also not the only manufacturer providing CAR-T drugs at a high price. And lastly, they offer alternative payment programmes to make the therapy more affordable. https://en.wikipedia.org/wiki/CAR_T_cell#Economics
> high manufacturing cost and the necessity for long hospital follow-up
The lead researcher behind the treatment claims the treatment cost under $20k to administer though, and I've never heard of mass production/adoption causing the cost of a product to go up in price (edit: excepting certain luxury goods that go up because they're a status symbol or something), certainly not >20x more... I know nothing about the medical field so I'm open to having my mind changed but that completely defies intuition. After seeing $450 bags of saline on a medical bill I had last year I'm much more inclined to believe they're just price gouging.
> Novartis is also not the only manufacturer providing CAR-T drugs at a high price.
I guess more than one company can do something despicable?
> offer alternative payment programmes
The "alternative payment programme" mentioned is "requiring payment only if the CAR T therapy induces a complete remission by a certain time point after treatment." I'd much rather pay $20k whether it succeeds or fails than $475k if it succeeds and $0 if it fails, if it fails I'm probably dead and don't care very much...
The lead researcher behind the treatment claims the treatment cost under $20k to administer though, and I've never heard of mass production/adoption causing the cost of a product to go up in price (edit: excepting certain luxury goods that go up because they're a status symbol or something), certainly not >20x more... I know nothing about the medical field so I'm open to having my mind changed but that completely defies intuition. After seeing $450 bags of saline on a medical bill I had last year I'm much more inclined to believe they're just price gouging.
> Novartis is also not the only manufacturer providing CAR-T drugs at a high price.
I guess more than one company can do something despicable?
> offer alternative payment programmes
The "alternative payment programme" mentioned is "requiring payment only if the CAR T therapy induces a complete remission by a certain time point after treatment." I'd much rather pay $20k whether it succeeds or fails than $475k if it succeeds and $0 if it fails, if it fails I'm probably dead and don't care very much...
Start listening from 46:30 You can hear how much does it cost in research phase, it would be much cheaper in mass production not more.
https://www.youtube.com/watch?v=jQfFCC6i5_o&t=2792s
I am sure pharma industry has similar excuses for why Epipen 10x expensive in America compared to other parts of the world.
https://www.youtube.com/watch?v=jQfFCC6i5_o&t=2792s
I am sure pharma industry has similar excuses for why Epipen 10x expensive in America compared to other parts of the world.
Killing cancer is very similar to killing weeds in agriculture, it's full of ̶r̶a̶n̶d̶o̶m̶ ̶m̶u̶t̶a̶t̶i̶o̶n̶ biodiversity that give it all sorts of potential. People get mutated cells all the time in their lifetime, but those cells get cleaned up because those cells don't have the proper mutations or circumstances to hide from the immune system.
It's rare enough to find a way kill an organism but leave a related one safe, like trying to target millet in tall fescue grown for seed, or targeting mites on honeybees. Usually it's actually just a small difference in tolerance between the two that you are exploiting. We are trying to kill a human within a human.
So what happens is that even if you wipe out 99.999% of the problem, it means the remaining portion of the pest had a genetic mutation that gave it increased resistance. So that's what will reproduce and you can't just increase the rate and try again. You are now just trying to stunt growth.
This is why cancer can be reduced below detection limits, only to have it re-emerge several months or years later and kill the patient because the treatment no longer could touch it. Monotherapies should never be utilized, because failure will eventually occur. Failure in agriculture only means herbicide resistant annual ryegrass or kochia, eventual economic damages, and regulation mandating cycling of modes of action. But Failure in cancer treatment means death and a family burdened by massive debt.
It should be noted that "cancer survival rates" are defined as the percent of people who survive a disease such as cancer *for a specified amount of time*. And I've noticed that the rates that get thrown around tend to range from a several months to just a few years. If a doctor manages to keep you alive and suffering for 2 years and a day before the cancer kills you, your "treatment success" gets added to X survival % (over two years)
I definitely welcome more tools to utilize, but there should always be some form of multi-therapy, a magic pill is a dangerous hope that doesn't understand the enemy.
Incidentally, look up Hyperthermia Therapy, it's less well known but pretty neat. It takes advantage that cancer cells aren't as robust to survive denaturing to begin with due to generally being in a low oxygen/blood environment (which limits detection by the immune system), but also that they are forced to either die or reopen their previously closed membrane transport systems which will now release chemical signals that the immune system can see as a problem. It's usually combined with chemicals that prime the immune system for "alertness". While this method isn't immune to resistance, it's able to exploit the very thing that the cancer needed to hide and survive.
It's rare enough to find a way kill an organism but leave a related one safe, like trying to target millet in tall fescue grown for seed, or targeting mites on honeybees. Usually it's actually just a small difference in tolerance between the two that you are exploiting. We are trying to kill a human within a human.
So what happens is that even if you wipe out 99.999% of the problem, it means the remaining portion of the pest had a genetic mutation that gave it increased resistance. So that's what will reproduce and you can't just increase the rate and try again. You are now just trying to stunt growth.
This is why cancer can be reduced below detection limits, only to have it re-emerge several months or years later and kill the patient because the treatment no longer could touch it. Monotherapies should never be utilized, because failure will eventually occur. Failure in agriculture only means herbicide resistant annual ryegrass or kochia, eventual economic damages, and regulation mandating cycling of modes of action. But Failure in cancer treatment means death and a family burdened by massive debt.
It should be noted that "cancer survival rates" are defined as the percent of people who survive a disease such as cancer *for a specified amount of time*. And I've noticed that the rates that get thrown around tend to range from a several months to just a few years. If a doctor manages to keep you alive and suffering for 2 years and a day before the cancer kills you, your "treatment success" gets added to X survival % (over two years)
I definitely welcome more tools to utilize, but there should always be some form of multi-therapy, a magic pill is a dangerous hope that doesn't understand the enemy.
Incidentally, look up Hyperthermia Therapy, it's less well known but pretty neat. It takes advantage that cancer cells aren't as robust to survive denaturing to begin with due to generally being in a low oxygen/blood environment (which limits detection by the immune system), but also that they are forced to either die or reopen their previously closed membrane transport systems which will now release chemical signals that the immune system can see as a problem. It's usually combined with chemicals that prime the immune system for "alertness". While this method isn't immune to resistance, it's able to exploit the very thing that the cancer needed to hide and survive.
>> Hyperthermia Therapy
So just go eat some salmonella at Chipotle to cure your cancer?
So just go eat some salmonella at Chipotle to cure your cancer?
This is apocryphal (I don’t have a direct source or cared quite enough to find one), but basically my understanding of the origins of the treatment was that it was noticed back when Britain was still an empire, you’d get these upper class guys with cancer heading off to some tropical place “for one last adventure”, and that some would somehow come back free of it.
Basically in addition to the environmental heat stress, they’d catch some horrible tropical disease and end up with a dangerously high fever. If they survived that then they found the cancerous lump on their neck or wherever would start shrinking.
These effects have been known and studied for quite a long while, but was broadly ignored until the past few decades. And even now it’s still not a well known phenomenon.
Back when I looked into it, it seems that regular sauna use may also be beneficial against cancer incidence, though there are a cascade of various things that go on under heat stress that can have positive effects. Prior to my current medication I found sitting in my vehicle in the sun and just miserably sweating it out for half and hour was a good way to “reset” myself for the day if I was having a bad depressive episode with an involuntary spiral of negative thoughts. I’d say it was just endorphins, but those don’t last all day.
Basically in addition to the environmental heat stress, they’d catch some horrible tropical disease and end up with a dangerously high fever. If they survived that then they found the cancerous lump on their neck or wherever would start shrinking.
These effects have been known and studied for quite a long while, but was broadly ignored until the past few decades. And even now it’s still not a well known phenomenon.
Back when I looked into it, it seems that regular sauna use may also be beneficial against cancer incidence, though there are a cascade of various things that go on under heat stress that can have positive effects. Prior to my current medication I found sitting in my vehicle in the sun and just miserably sweating it out for half and hour was a good way to “reset” myself for the day if I was having a bad depressive episode with an involuntary spiral of negative thoughts. I’d say it was just endorphins, but those don’t last all day.
> But Failure in cancer treatment means death and a family burdened by massive debt.
The latter is, among developed countries, only true in the US.
The latter is, among developed countries, only true in the US.
All you have to do is add "... in rats" to most headlines of this nature, and it will tell you all you need to know, at least for the moment.
Rats is probably an improvement over the usual mice. Rats actually naturally have very high cancer rates… in captivity rats live an absolute max of 2 years, and about 80% of them will die because of some sort of cancer.
In the wild it’s less so, but only because the average lifespan is less than a year (predation, traps, etc).
In the wild it’s less so, but only because the average lifespan is less than a year (predation, traps, etc).
He refers to the objective fact that the rodent veterinary field is making great advances, while human medicine continues to stagnate, as the cross of the time has shown that rodent treatments hardly ever works in humans.
I suggest then, complete biological mappings of the human being (big words), the same way does exist ADN human mappings, for being able to run simulations in the same way the physics field is constantly doing.
I see a world, were one goes to the doctor, takes an ADN sample, and a biological map is correlated, were to see if the prescribed drugs interacts well or bad between them thanks to this mappings, at same time the research teams run simulations for to find quickly possible cures to the targeted sickness by isolating common patterns in different biological mappings (different human key ADN structures).
I suggest then, complete biological mappings of the human being (big words), the same way does exist ADN human mappings, for being able to run simulations in the same way the physics field is constantly doing.
I see a world, were one goes to the doctor, takes an ADN sample, and a biological map is correlated, were to see if the prescribed drugs interacts well or bad between them thanks to this mappings, at same time the research teams run simulations for to find quickly possible cures to the targeted sickness by isolating common patterns in different biological mappings (different human key ADN structures).
Rats do not live an absolute max of 2 years in captivity.
Sounds like there’s human trials in motion already?
You can usually add that or "in California" on all the bad and dangerous stuff.
[dupe]
Discussion over here: https://news.ycombinator.com/item?id=36960895
Discussion over here: https://news.ycombinator.com/item?id=36960895
Obligatory XKCD: https://xkcd.com/1217/
However, the therapy is in Phase I clinical trials (only really looking at safety and maximum tolerated dose). Not a randomized control trial and unlikely to show efficacy unless it has near magical properties.
However, the therapy is in Phase I clinical trials (only really looking at safety and maximum tolerated dose). Not a randomized control trial and unlikely to show efficacy unless it has near magical properties.
It was in rats, that one doesn't fit.
[deleted]
I thought you meant the other one :/ https://xkcd.com/931/
That one is heartbreaking. Actually all those about his girlfriend‘s cancer, but that one really made me understand what a shitshow cancer is.
A handgun kills cancer in vivo, too... but the risk to the host is intolerably great.
'Cancer-killing pill' is now being tested on humans
https://news.ycombinator.com/item?id=36969500 (12 hours ago, 33 comments)
Cancer pill AOH1996 shows promise in annihilating all solid tumours
https://news.ycombinator.com/item?id=36960895 (1 day ago, 19 comments)
Cancer pill AOH1996 shows promise in annihilating all solid tumours
https://news.ycombinator.com/item?id=36960292 (1 day ago, 16 comments)