6 ms·

OK, somebody please ruin my excitement now and tell me how this isn’t a miracle cancer cure.

CamperBob2 3y ago
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.
- TylerE 3y ago
  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).
  - emptysongglass 3y ago
    Rats do not live an absolute max of 2 years in captivity.
  - drtgh 3y ago
    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).
- entropy273 3y ago
  Sounds like there’s human trials in motion already?
  - adamredwoods 3y ago
    Yes. https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2021-14102&r=1 https://www.cancer.gov/about-cancer/treatment/clinical-trial...
- Tao3300 3y ago
  You can usually add that or "in California" on all the bad and dangerous stuff.
bglazer 3y ago
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
serguzest 3y ago
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-has-approved-the-first-gene-therapy-for-cancer/ https://www.technologyreview.com/2017/08/30/149399/the-fda-h... https://landdestroyer.blogspot.com/2017/08/big-pharma-novartis-to-charge-475000.html https://landdestroyer.blogspot.com/2017/08/big-pharma-novart...
- ldhough 3y ago
  Well this is despicable...
  - klmr 3y ago
    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 https://en.wikipedia.org/wiki/CAR_T_cell#Economics
    - serguzest 3y ago
      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 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.
    - ldhough 3y ago
      > 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...
adamredwoods 3y ago
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://pubmed.ncbi.nlm.nih.gov/29967249/ https://news.ucr.edu/articles/2019/10/02/research-focus-small-molecule-can-help-fight-breast-cancer 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/S2451-9456(23)00221-0 https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...
Modified3019 3y ago
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.
- 3y ago

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.

TylerE 3y ago
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).
- emptysongglass 3y ago
  Rats do not live an absolute max of 2 years in captivity.
- drtgh 3y ago
  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).
entropy273 3y ago
Sounds like there’s human trials in motion already?
- adamredwoods 3y ago
  Yes. https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2021-14102&r=1 https://www.cancer.gov/about-cancer/treatment/clinical-trial...
Tao3300 3y ago
You can usually add that or "in California" on all the bad and dangerous stuff.

bglazer 3y ago

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

serguzest 3y ago

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-has-approved-the-first-gene-therapy-for-cancer/ https://www.technologyreview.com/2017/08/30/149399/the-fda-h... https://landdestroyer.blogspot.com/2017/08/big-pharma-novartis-to-charge-475000.html https://landdestroyer.blogspot.com/2017/08/big-pharma-novart...

ldhough 3y ago
Well this is despicable...
- klmr 3y ago
  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 https://en.wikipedia.org/wiki/CAR_T_cell#Economics
  - serguzest 3y ago
    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 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.
  - ldhough 3y ago
    > 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...

adamredwoods 3y ago

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://pubmed.ncbi.nlm.nih.gov/29967249/ https://news.ucr.edu/articles/2019/10/02/research-focus-small-molecule-can-help-fight-breast-cancer 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/S2451-9456(23)00221-0 https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...

Modified3019 3y ago

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.

3y ago