4 ms·

Curing brain tumors: blocking functions in cells with a docked molecule

94 points by wglb 3y ago

swader999 3y ago
So about ten years to significant human trials. Be dubious of any headline with "cure" in it. I remember when reovirus and modified adenovirus were supposed to be the ticket for glio. Such a terrible thing, hope this is faster to the mark than my jaded forecast.
- haldujai 3y ago
  “Cure” with GBM is a very lofty goal but the first phase II oncolytic virus trial was actually quite promising! 2 year survival doesn’t sound like a lot but considering the study included non-mutated GBM (the worst kind) this prognosis is ~3-4x longer than with current treatment options. GBM (IDH-wt) is, unfortunately, extremely aggressive and not uncommon. Arguably the worst type of cancer for an adult. As a small silver lining the dismal prognosis means experimental therapies are possible on compassionate grounds and trials are expedited. We’ve also gotten much better as histologically and radiologically evaluating the disease. I’m cautiously optimistic it won’t be the immediate death sentence it currently is within my career, but it does appear we are still a few breakthroughs away from that being possible. https://www.nature.com/articles/s41591-022-01897-x https://www.nature.com/articles/s41591-022-01897-x
  - swader999 3y ago
    I heard one surgeon describe operating on glio similar to trying to remove cottage cheese that's been randomly mixed in to a tub of margarine. You have to get it out without disturbing or taking out too much of the margarine.
chrisamiller 3y ago
I hate to be that guy, because it seems like there is some interesting science behind this press release hype. There are, however, many many miles between "effects in a mouse model" and "human therapeutic", let alone "cure". I wish them the best of luck as they consider safety and efficacy in clinical trials.
- BenFranklin100 3y ago
  Correct. However, research models like mice play a critical role in revealing key mechanisms of actions for many diseases. One can crudely think of it as a reverse engineering challenge - picking apart the key functions and program flow from obfuscated object code. Not all of the program logic or functions will have 1-1 correlates to humans, but these models can provide important clues for new therapeutics that might work in people. These types of experiments simply can’t ethically be done in humans. And I entirely agree with your other point: university press releases are notorious for hyping research. It does the biomedical field a disservice, and gives the impression clinical trials are but an afterthought. Nothing could be further from the truth.
  - chrisamiller 3y ago
    I do cancer research, including using mouse models, so believe me, I know the difficulty :-) Getting promising drugs into humans is -hard-, and this research is interesting, but this press release is still kind of shitty.
davisr 3y ago
Mebendazole and fenbendazole, antihelmintics, have also shown effective against gioblastoma and other types of cancer. Mebendazole, and others in its family, are also involved in a broken healthcare system in the US, where these medications costs between $0.07 and $10.00 per tablet in every other country, but there is a monopoly on manufacture that can price these tablets at $350 per tablet.
- JPLeRouzic 3y ago
  $6.52 in Belgium: https://www.pharmachezvous.be/medicaments/vermifuge/vermox-comp-6x100mg-2/ https://www.pharmachezvous.be/medicaments/vermifuge/vermox-c...
- meindnoch 3y ago
  Surely, if glioblastoma (the most aggressive form of brain cancer) could be cured with such simple anti-parasite medications, we'd be hearing about people curing themselves... This sounds like covid-19 and ivermectin.
  - ekianjo 3y ago
    Dont underestimate the level of corruption in the existing system
    - _Microft 3y ago
      They said that people would experiment with these drugs on themselves to cure their cancer (assuming that these drugs were actually as effective as claimed). There seems no obvious system involved in this. Which system do you mean?
      - davisr 3y ago
        The system that won't spend millions of dollars to repurpose (and re-certify) generic drugs with the FDA...drugs that already have off-label uses for treating cancer. https://www.nytimes.com/2020/02/25/opinion/repurposing-drugs-cancer.html https://www.nytimes.com/2020/02/25/opinion/repurposing-drugs...
methodical 3y ago
Seeing stuff like this is always a bit bitter-sweet. Ignoring the fact that obviously this is a far way from a "cure" in adults, as this is an early stage study, I always feel like seeing how far and how fast we're progressing on these types of diseases just makes me more anxious about being a bit too early. While I think FOMO is a bit of a poor way to put it, since there has been significant advancement within our time, I can't help but think how awful it'd be to get a disease of this caliber in current year knowing that given an extra 10-20 years, you'd like have a much better prognosis. Maybe I'm just over-thinking it here, but even with a less severe and more common cancer, I think the thing I'd struggle the most with would be the unfortunate timing. Perhaps this is insensitive or moronic, but it's been something I've always thought about when I've read about these advancements in the field of cancer treatments. Would be curious to hear how others feel about it, and whether anybody else has this FOMO feeling (for lack of a better description)?
- penteract 3y ago
  Having had cancer recently, I felt the opposite: happy that the prognosis for many cancers is dramatically better than it was a few decades ago. On the other hand, it has made me aware that for many people with cancer, news about developments in cancer treatment feels like a matter of personal life and death, even if it's usually not relevant to their specific type of cancer, and not likely to be ready in time to result in any change to their treatment.
- graypegg 3y ago
  I guess that’s the difficulty of living on an exponential curve. It’s always going to be better tomorrow but today is much better than yesterday!
- m463 3y ago
  moreso when you've lost a family member to glioblastoma. And II've lost other family members to other maladies, and when I read of causes discovered and treatments offered, the only sane thought is that new present-day cases will fare better.
Octokiddie 3y ago
This was a mouse study with a molecule whose human effects are largely unknown. Interesting research, but likely far away from anything that will treat humans. That said, the bar for human glioblastoma trials is very low. There is no cure and the disease is 100% fatal. After the standard of care treatment (which hasn't changed in 10 years), patients enter a period of regular brain scans, waiting for the inevitable recurrence and the next step down in quality of life.
- haldujai 3y ago
  > After the standard of care treatment (which hasn't changed in 10 years) A lot has changed in 10 years for the 'standard of care' conventional treatments (RT + TMZ) although most active-treatment GBM cases will actually be on some experimental therapy/clinical trial. In fact, the WHO classification was only recently updated (2021) as what we were calling GBM included different types of gliomas with very different prognostic implications. Unfortunately, as you allude to, despite several advancements prognosis has only marginally improved over 10 years. The main issue is that these patients almost always present with symptoms (like seizures) by which point curative intent ablative therapies (radiation or surgery) are no longer possible due to intolerable side effects. > waiting for the inevitable recurrence It's more progression than recurrence, there is (essentially) always residual disease with GBM even after radiotherapy/surgery which is one of the main reasons it remains so fatal (~6-9 months). Because of the blood-brain barrier chemotherapeutic options are also very limited.
- tingletech 3y ago
  When my Dad had glioblastoma, I remember seeing an ad for a custom vaccine that could be created for brain tumors. "Save the tissue, save your life" or something like that was the headline slogan it had, and it was saying to ask your brain surgeon to save your tumor so they could make your personalized treatment from it. It conjured an image that has stuck with me of someone on a gurney screaming that out as their last words before going under from anesthesia. Hopefully something I don't ever need to remember at a critical moment.
ablyveiled 3y ago
Brain cancer can also be regulated with diet, at least in some instances. https://www.braintumourresearch.org/stories/in-hope/in-hope-stories/andrew-scarborough https://www.braintumourresearch.org/stories/in-hope/in-hope-...
dp-hackernews 3y ago
You've Been Lied to about CANCER!!! [with Dr Thomas Seyfried, PhD] https://www.youtube.com/watch?v=EN58tZ6dspA https://www.youtube.com/watch?v=EN58tZ6dspA

94 points by wglb 3y ago

So about ten years to significant human trials. Be dubious of any headline with "cure" in it. I remember when reovirus and modified adenovirus were supposed to be the ticket for glio. Such a terrible thing, hope this is faster to the mark than my jaded forecast.

haldujai 3y ago
“Cure” with GBM is a very lofty goal but the first phase II oncolytic virus trial was actually quite promising! 2 year survival doesn’t sound like a lot but considering the study included non-mutated GBM (the worst kind) this prognosis is ~3-4x longer than with current treatment options. GBM (IDH-wt) is, unfortunately, extremely aggressive and not uncommon. Arguably the worst type of cancer for an adult. As a small silver lining the dismal prognosis means experimental therapies are possible on compassionate grounds and trials are expedited. We’ve also gotten much better as histologically and radiologically evaluating the disease. I’m cautiously optimistic it won’t be the immediate death sentence it currently is within my career, but it does appear we are still a few breakthroughs away from that being possible. https://www.nature.com/articles/s41591-022-01897-x https://www.nature.com/articles/s41591-022-01897-x
- swader999 3y ago
  I heard one surgeon describe operating on glio similar to trying to remove cottage cheese that's been randomly mixed in to a tub of margarine. You have to get it out without disturbing or taking out too much of the margarine.

chrisamiller 3y ago

I hate to be that guy, because it seems like there is some interesting science behind this press release hype. There are, however, many many miles between "effects in a mouse model" and "human therapeutic", let alone "cure". I wish them the best of luck as they consider safety and efficacy in clinical trials.

BenFranklin100 3y ago
Correct. However, research models like mice play a critical role in revealing key mechanisms of actions for many diseases. One can crudely think of it as a reverse engineering challenge - picking apart the key functions and program flow from obfuscated object code. Not all of the program logic or functions will have 1-1 correlates to humans, but these models can provide important clues for new therapeutics that might work in people. These types of experiments simply can’t ethically be done in humans. And I entirely agree with your other point: university press releases are notorious for hyping research. It does the biomedical field a disservice, and gives the impression clinical trials are but an afterthought. Nothing could be further from the truth.
- chrisamiller 3y ago
  I do cancer research, including using mouse models, so believe me, I know the difficulty :-) Getting promising drugs into humans is -hard-, and this research is interesting, but this press release is still kind of shitty.

davisr 3y ago

Mebendazole and fenbendazole, antihelmintics, have also shown effective against gioblastoma and other types of cancer. Mebendazole, and others in its family, are also involved in a broken healthcare system in the US, where these medications costs between $0.07 and $10.00 per tablet in every other country, but there is a monopoly on manufacture that can price these tablets at $350 per tablet.

JPLeRouzic 3y ago
$6.52 in Belgium: https://www.pharmachezvous.be/medicaments/vermifuge/vermox-comp-6x100mg-2/ https://www.pharmachezvous.be/medicaments/vermifuge/vermox-c...
meindnoch 3y ago
Surely, if glioblastoma (the most aggressive form of brain cancer) could be cured with such simple anti-parasite medications, we'd be hearing about people curing themselves... This sounds like covid-19 and ivermectin.
- ekianjo 3y ago
  Dont underestimate the level of corruption in the existing system
  - _Microft 3y ago
    They said that people would experiment with these drugs on themselves to cure their cancer (assuming that these drugs were actually as effective as claimed). There seems no obvious system involved in this. Which system do you mean?
    - davisr 3y ago
      The system that won't spend millions of dollars to repurpose (and re-certify) generic drugs with the FDA...drugs that already have off-label uses for treating cancer. https://www.nytimes.com/2020/02/25/opinion/repurposing-drugs-cancer.html https://www.nytimes.com/2020/02/25/opinion/repurposing-drugs...

methodical 3y ago

Seeing stuff like this is always a bit bitter-sweet. Ignoring the fact that obviously this is a far way from a "cure" in adults, as this is an early stage study, I always feel like seeing how far and how fast we're progressing on these types of diseases just makes me more anxious about being a bit too early. While I think FOMO is a bit of a poor way to put it, since there has been significant advancement within our time, I can't help but think how awful it'd be to get a disease of this caliber in current year knowing that given an extra 10-20 years, you'd like have a much better prognosis. Maybe I'm just over-thinking it here, but even with a less severe and more common cancer, I think the thing I'd struggle the most with would be the unfortunate timing. Perhaps this is insensitive or moronic, but it's been something I've always thought about when I've read about these advancements in the field of cancer treatments. Would be curious to hear how others feel about it, and whether anybody else has this FOMO feeling (for lack of a better description)?

penteract 3y ago
Having had cancer recently, I felt the opposite: happy that the prognosis for many cancers is dramatically better than it was a few decades ago. On the other hand, it has made me aware that for many people with cancer, news about developments in cancer treatment feels like a matter of personal life and death, even if it's usually not relevant to their specific type of cancer, and not likely to be ready in time to result in any change to their treatment.
graypegg 3y ago
I guess that’s the difficulty of living on an exponential curve. It’s always going to be better tomorrow but today is much better than yesterday!
m463 3y ago
moreso when you've lost a family member to glioblastoma. And II've lost other family members to other maladies, and when I read of causes discovered and treatments offered, the only sane thought is that new present-day cases will fare better.

Octokiddie 3y ago

This was a mouse study with a molecule whose human effects are largely unknown. Interesting research, but likely far away from anything that will treat humans. That said, the bar for human glioblastoma trials is very low. There is no cure and the disease is 100% fatal. After the standard of care treatment (which hasn't changed in 10 years), patients enter a period of regular brain scans, waiting for the inevitable recurrence and the next step down in quality of life.

haldujai 3y ago
> After the standard of care treatment (which hasn't changed in 10 years) A lot has changed in 10 years for the 'standard of care' conventional treatments (RT + TMZ) although most active-treatment GBM cases will actually be on some experimental therapy/clinical trial. In fact, the WHO classification was only recently updated (2021) as what we were calling GBM included different types of gliomas with very different prognostic implications. Unfortunately, as you allude to, despite several advancements prognosis has only marginally improved over 10 years. The main issue is that these patients almost always present with symptoms (like seizures) by which point curative intent ablative therapies (radiation or surgery) are no longer possible due to intolerable side effects. > waiting for the inevitable recurrence It's more progression than recurrence, there is (essentially) always residual disease with GBM even after radiotherapy/surgery which is one of the main reasons it remains so fatal (~6-9 months). Because of the blood-brain barrier chemotherapeutic options are also very limited.
tingletech 3y ago
When my Dad had glioblastoma, I remember seeing an ad for a custom vaccine that could be created for brain tumors. "Save the tissue, save your life" or something like that was the headline slogan it had, and it was saying to ask your brain surgeon to save your tumor so they could make your personalized treatment from it. It conjured an image that has stuck with me of someone on a gurney screaming that out as their last words before going under from anesthesia. Hopefully something I don't ever need to remember at a critical moment.

ablyveiled 3y ago

Brain cancer can also be regulated with diet, at least in some instances. https://www.braintumourresearch.org/stories/in-hope/in-hope-stories/andrew-scarborough https://www.braintumourresearch.org/stories/in-hope/in-hope-...

dp-hackernews 3y ago

You've Been Lied to about CANCER!!! [with Dr Thomas Seyfried, PhD] https://www.youtube.com/watch?v=EN58tZ6dspA https://www.youtube.com/watch?v=EN58tZ6dspA