Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Breast Cancer(mdpi.com)
mdpi.com
Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Breast Cancer
https://www.mdpi.com/2076-393X/12/9/958#
89 comments
Definitely eyebrow raising but I'm always a fan of a bit of "mad scientist" self-experimentation (within reason), whether it be Barry Marshall chugging H. pylori or Thought Emporium giving himself lactase gene therapy.
I think it's pretty great. Put your mouth where your money is sort of thing.
Agree. This is one of the first things I thought, and while I'm not super well versed in the processes behind getting clinical experiments approved, I can see how the data might not account for confounders that you'd see in a traditional clinical study
So the treatment worked, and she appears to be recovered from what might otherwise have been treatment-resistant, fatal cancer.
But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
But she was only able to do so because of having the skill and access needed to self-administer the cure. How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
What doesn't make its way into case studies and HN headlines is all the stories of people who did get access to uncertain treatments and died anyway. Sometimes faster than they would have without the experimental treatment at all.
This isn't a case study about a breast cancer cure. This is a story about a single individual's cancer's response to an experimental treatment. For comparison, there are case studies of spontaneous remission in refractory cancers triggered by seasonal flu.
Virologists aren't sitting around waiting to develop cancer before they decide to roll out the miracle cancer cures. Oncolytic viruses have been researched, studied and tested on cancer patients for almost a century now.
This isn't a case study about a breast cancer cure. This is a story about a single individual's cancer's response to an experimental treatment. For comparison, there are case studies of spontaneous remission in refractory cancers triggered by seasonal flu.
Virologists aren't sitting around waiting to develop cancer before they decide to roll out the miracle cancer cures. Oncolytic viruses have been researched, studied and tested on cancer patients for almost a century now.
> Virologists aren't sitting around waiting to develop cancer before they decide to roll out the miracle cancer cures.
You say that, but the article suggests otherwise. This virologist did believe that her colleagues were sitting around not rolling out something that would cure her. It is pretty easy to see how a lot of cures would be stuck in the research world, unable to get to patients; there is no reason to believe they are moving quickly to bring cures to market. You can see people arguing up and down the thread how they have higher priorities than testing stuff to see if it might work.
You say that, but the article suggests otherwise. This virologist did believe that her colleagues were sitting around not rolling out something that would cure her. It is pretty easy to see how a lot of cures would be stuck in the research world, unable to get to patients; there is no reason to believe they are moving quickly to bring cures to market. You can see people arguing up and down the thread how they have higher priorities than testing stuff to see if it might work.
> This virologist did believe that her colleagues were sitting around not rolling out something that would cure her.
And because her outcome was so unexpected and unusual it got published as a case study. What you don't see are all the cases where the experimental miracle cure treatment did not work. What you also won't see in headlines are all the trials where putative miracle cures and other promising treatments failed to demonstrate survival benefits in larger cohorts than 1.
One of the counterintuitive things about cancer is how badly individual cases and responses to treatment generalize to the broader patient population. If you didn't know any better, you could easily read a story like this and think "wow, this breast cancer cure was just stuck in a lab somewhere!" But to put a story like this into context, you need to understand just how many individual miracle remission stories there are, and how varied individual cancers and responses to treatment are.
There are potential miracle cures almost everywhere, and a large number of them are being aggressively researched, tested on cancer patients at any given time - often as part of combination therapies. Some of these promising technologies do become breakthrough cancer treatments that create durable remissions, such as checkpoint inhibitors. The rest fizzle out.
And because her outcome was so unexpected and unusual it got published as a case study. What you don't see are all the cases where the experimental miracle cure treatment did not work. What you also won't see in headlines are all the trials where putative miracle cures and other promising treatments failed to demonstrate survival benefits in larger cohorts than 1.
One of the counterintuitive things about cancer is how badly individual cases and responses to treatment generalize to the broader patient population. If you didn't know any better, you could easily read a story like this and think "wow, this breast cancer cure was just stuck in a lab somewhere!" But to put a story like this into context, you need to understand just how many individual miracle remission stories there are, and how varied individual cancers and responses to treatment are.
There are potential miracle cures almost everywhere, and a large number of them are being aggressively researched, tested on cancer patients at any given time - often as part of combination therapies. Some of these promising technologies do become breakthrough cancer treatments that create durable remissions, such as checkpoint inhibitors. The rest fizzle out.
I'd suggest this virologist actually does understand her field quite well. You're in the awkward position of arguing that an expert in a field doesn't understand what she is doing while citing evidence to support yourself that you (by construction) don't have. It is equally likely - actually quite a bit more likely - that we do have a huge number of improvements over current best-practice stuck in labs because people are insisting on damaging levels of certainty rather than letting people try things. This woman seemed fairly confident that she could achieve an improvement on clinical best practice.
There are risks, but having cancer is a risky business right from the get go.
There are risks, but having cancer is a risky business right from the get go.
I notice you've watered down your terminology from "cure" to "improvement on clinical best practice" which are pretty different things in the context of cancer treatment. However, I can respect the switch and I'll treat it as a sign you're starting to treat the subject a bit more seriously. It's more accurate to the outcome in the case study, too, since treatment was locoregional and neoadjuvant only. Full remission was only achieved with the traditional interventions of surgery and adjuvant targeted therapy.
> You're in the awkward position of arguing that an expert in a field doesn't understand what she is doing while citing evidence to support yourself that you (by construction) don't have.
No. I'm in the non-awkward position of arguing that non-experts should be careful about interpreting a single case study without context. Especially in a way that implies miracle cancer cures are sitting around in labs with no one paying any attention to them.
I don't think the average HN reader understands just how many wildly different treatments, drugs and therapies are being thrown at different cancers and how quickly medical oncology moves as a field. Cancers are an extremely complex family of diseases. Early results and case studies are correspondingly extremely difficult to interpret due to the variation in individual responses and disease course.
The existence of a "miracle" cancer treatment is almost ruled out from first principles. But if such a miracle treatment is sitting around in a lab, it would be non-trivial to tell it apart from the thousands of other promising candidate therapies that go on to pan out to nothing.
> You're in the awkward position of arguing that an expert in a field doesn't understand what she is doing while citing evidence to support yourself that you (by construction) don't have.
No. I'm in the non-awkward position of arguing that non-experts should be careful about interpreting a single case study without context. Especially in a way that implies miracle cancer cures are sitting around in labs with no one paying any attention to them.
I don't think the average HN reader understands just how many wildly different treatments, drugs and therapies are being thrown at different cancers and how quickly medical oncology moves as a field. Cancers are an extremely complex family of diseases. Early results and case studies are correspondingly extremely difficult to interpret due to the variation in individual responses and disease course.
The existence of a "miracle" cancer treatment is almost ruled out from first principles. But if such a miracle treatment is sitting around in a lab, it would be non-trivial to tell it apart from the thousands of other promising candidate therapies that go on to pan out to nothing.
> I don't think the average HN reader understands just how many wildly different treatments, drugs and therapies are being thrown at different cancers
You say that as though it supports your thesis, but you obviously haven't thought thorough the implications if you don't believe there are a bunch of cures sitting around in labs.
You still can't deal with the main weakness in your argument here - this woman, who is very close to the pointy end of the stick and qualified enough, is evidence that the virology world is in fact sitting around on some fairly important techniques that could help cure her. Which is pretty much what we would expect given that taking something from the lab to the other side of the regulators involves enormous costs and demands of rigour.
And you seem a bit too focused on miracle cures. I suggest discarding that focus, miracles generally imply that something is impossible or unlikely. It is better to focus on realities and probable outcomes.
You say that as though it supports your thesis, but you obviously haven't thought thorough the implications if you don't believe there are a bunch of cures sitting around in labs.
You still can't deal with the main weakness in your argument here - this woman, who is very close to the pointy end of the stick and qualified enough, is evidence that the virology world is in fact sitting around on some fairly important techniques that could help cure her. Which is pretty much what we would expect given that taking something from the lab to the other side of the regulators involves enormous costs and demands of rigour.
And you seem a bit too focused on miracle cures. I suggest discarding that focus, miracles generally imply that something is impossible or unlikely. It is better to focus on realities and probable outcomes.
The counter-argument is "how many more would die if we just let desperate people yolo on themselves." Which brings us back to the current compromise solutions.
We probably should let them if they’ve exhausted other options right?
I think the main worry is scam artists who essentially pray on desperate people with "cures" that do nothing at best and shorten their lives at worse.
I'm fine with letting people try whatever they want if there are no other options (their life, although informed consent is tricky) however i dont think we should allow marketing such things to patients or allow anyone making money off it.
I'm fine with letting people try whatever they want if there are no other options (their life, although informed consent is tricky) however i dont think we should allow marketing such things to patients or allow anyone making money off it.
There are already plenty of people who promote scam cures. We shouldn't deny potentially useful treatments to patients in dire need just to reduce somewhat the business of scammers.
Detect and punish scammers if they are an issue. Allow people to take risky medical treatments if they have serious incurable illnesses.
Detect and punish scammers if they are an issue. Allow people to take risky medical treatments if they have serious incurable illnesses.
You're not adding money to the mix.
If a company or research group wants to sponsor an experimental treatment with patient approval and waiver free of charge, that's one thing.
But they almost immediately turn around and say " oh we'll need to cover costs..." and suddenly the incentive is very different.
If a company or research group wants to sponsor an experimental treatment with patient approval and waiver free of charge, that's one thing.
But they almost immediately turn around and say " oh we'll need to cover costs..." and suddenly the incentive is very different.
Exactly. They should be able to take whatever experimental drugs might be available.
The problem is, how do companies identify these patients or how do patients identify these companies without leaving room for massive abuse.
Maybe the treatments have to be zero cost? That feels like it would eliminate all bad actors?
The problem is, how do companies identify these patients or how do patients identify these companies without leaving room for massive abuse.
Maybe the treatments have to be zero cost? That feels like it would eliminate all bad actors?
That’s actually kinda a great idea imo
All other considerations aside, the technical detail defining this case is that she administered herself this treatment before other options. Which made all the difference, and which makes it not an option "if they've exhausted other options"...
Let them what? Enroll in a clinical trial? Buy drugs from some website?
Get a PhD to try and cure their own disease?
https://www.wired.com/story/sleep-no-more-crusade-genetic-ki...
Get a PhD to try and cure their own disease?
https://www.wired.com/story/sleep-no-more-crusade-genetic-ki...
I believe the main point is to allow the patient to choose from a set of treatments. Correct me if I’m wrong, but isn’t this already happening at some level, where patients receive treatments that are in advanced stages of drug trials?
I imagine there could be other options available, and many times the issues are related to logistics, bureaucracy, and corruption. For instance, many people around the world go hungry due to logistical challenges (e.g., political interference) [1].
It seems we accept the status quo, while some companies are sending cheaper spacecraft into space.
[1] https://www.reddit.com/r/NoStupidQuestions/comments/zye4gm/w...
I imagine there could be other options available, and many times the issues are related to logistics, bureaucracy, and corruption. For instance, many people around the world go hungry due to logistical challenges (e.g., political interference) [1].
It seems we accept the status quo, while some companies are sending cheaper spacecraft into space.
[1] https://www.reddit.com/r/NoStupidQuestions/comments/zye4gm/w...
People can enroll in clinical trials.
https://clinicaltrials.gov/
https://clinicaltrials.gov/
That page is for information, not for enrolling.
Each study tells if they are recruiting.
Then you can drill down and see locations where they are recruiting. For example,
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
Then you can drill down and see locations where they are recruiting. For example,
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
Health care is not a farmer’s market. You don’t pick from ten different kinds of potatoes. There will be tons of people with magic treatments with no statistical evidence or even fraudulent data. Snake oil, literally. Net negative for society.
Sure, but when someone reaches the final stages of life, the logic shifts. This is similar to the debate around euthanasia: do individuals have the right to end their lives or choose alternative treatments, even without strong statistical backing? Your comment also raises another important question: does the "net negative for society" truly matter in these cases? That's a political perspective, and like euthanasia, it's subject to debate.
I respectfully disagree. Selling desperate people fraudulent stuff for real money will never not be net negative for society in my view.
I am firmly against selling fraudulent products to people, but I also believe there are ways to introduce unconventional treatments, like those from an 'irreverent Dr. House.'. I think regulations should evolve to keep pace with the acceleration of science, as seen when the COVID vaccine was developed swiftly in response to urgent needs.
Exhausting all treatment options is not the same as having nothing to close.
There's no shortage of cancer patients at end-of-life stage undergoing aggressive treatments and/or experimental therapies in clinical trials for minimal to no survival benefit. For almost all of these patients, the best option for them and their loved ones will end up having been a palliative or best supportive care model.
There's no shortage of cancer patients at end-of-life stage undergoing aggressive treatments and/or experimental therapies in clinical trials for minimal to no survival benefit. For almost all of these patients, the best option for them and their loved ones will end up having been a palliative or best supportive care model.
But despite this, isn’t it their right to try in the hope that they can be the lucky one to get more years of life?
Once you've actually exhausted all other options, even a treatment that works probably won't save your life. Breakthrough treatments usually make a bigger difference when the conventional 5-year survival rate is around 20%, not 0%. Most "broad-spectrum" cancer treatments (radiation, cell division inhibitors, surgery) tend to cause permanent damage to multiple organs.
You can't see any externality risks to nonconsenters of having people use unapproved viruses on themselves sold from hucksters on TV infomercials and stuff?
Easy, don’t let hucksters make TV infomercials promoting their snake oil.
Saving people from themselves is a suspicious reason for anything.
That’s something only a hardcore blindsided liberal would say. My grandma (RIP) most definitely needed that for a few years before she died.
People spend billions on homeopathy, so... is it?
The placebo effect is real.
And why would you need to spend billions then? And why would you need to buy anything but a sugar pill instead of some unproven bs which is completely unregulated and might be something from glass clippings to something that could genuinely hurt you?
These same arguments get trotted out every time someone wants to defend very stupid practices and they have no teeth.
These same arguments get trotted out every time someone wants to defend very stupid practices and they have no teeth.
Identifying homeopathy as a case where less freedom would benefit someone is not sufficient to argue that it's a better policy.
Everyone who laughs so confidently at homeopathy, would likely do the same for a cutting edge treatment, which has yet to be widely recognized as effective. And in that case a lack of freedom would lead to a worse outcome.
Everyone who laughs so confidently at homeopathy, would likely do the same for a cutting edge treatment, which has yet to be widely recognized as effective. And in that case a lack of freedom would lead to a worse outcome.
That's complete hogwash. Homeopathy's core idea is that you can magically negate a poison by diluting it billions or trillions of times into a cure usually to the point where there's no detectable component anyway.
Experimental treatments definitely invite skepticism, and should. Humans can generally contain more than one level of skepticism - this treatment has a certain rate of failure, this treatment is unproven, and important, this treatment has no mechanism that could work and is a scam meant to separate a fool from his money.
Experimental treatments definitely invite skepticism, and should. Humans can generally contain more than one level of skepticism - this treatment has a certain rate of failure, this treatment is unproven, and important, this treatment has no mechanism that could work and is a scam meant to separate a fool from his money.
Easy: Zero. What you describe as "desperate people" are people who would already die without "yolo[ing] on themselves", so, by definition, the worst outcome is that they still die.
Precisely the same number as would have died from terminal disease anyway ?
The same? Desperate people yoloing in themselves is the number of people. regulating this sector instead of just keeping out the quacks was a thorough mistake .
Regulation is the mechanism by which quacks are filtered out of the healthcare industry. It is hardly foolproof (see lecanemab).
There is a lot of leeway (in the US) for treatment of terminal diseases with the Right to Try Act:
https://www.fda.gov/patients/learn-about-expanded-access-and...
https://www.fda.gov/patients/learn-about-expanded-access-and...
And unfortunately, that leads to a lot of wasted money. It's practically a scam, preying on the helpless.
It’s a scam to be able to try experimental treatments for your otherwise fatal disease?
There's a fairly obvious trade off here. Experimental treatments are often crap. But occasionally they're the thing that will be the standard in ten years, and only isn't now because it hasn't been thoroughly studied. Except that if you don't get it now you'll be dead in ten years.
This is the heart of the difference between freedom and paternalism. If people can choose for themselves then 90% of the time it's going to be ineffective, if not an outright scam. But if people can't choose for themselves then 100% of the time they die. The paternalists say it should be the latter, because scams are bad.
This is the heart of the difference between freedom and paternalism. If people can choose for themselves then 90% of the time it's going to be ineffective, if not an outright scam. But if people can't choose for themselves then 100% of the time they die. The paternalists say it should be the latter, because scams are bad.
The hazard here is in the nature of scams and how they propagate.
Let's suppose in the base case - experimental treatments are largely suppressed and difficult to access - the odds are 10:1. That's a 10% chance of significantly prolonged survival, against 90% ineffective. And some of those "ineffective", maybe ten or twenty percent, will be actively harmful: shorter survival or a nastier death.
Unchecked, though, scammers will proliferate, and the odds get worse. Because incurable illnesses are, relatively speaking, very common compared to 10% shots at curing them. (If the reverse were true, we'd have eliminated many more of them with a shotgun approach). So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
And that's before we even factor money - and financial harm not just to the patient but to their family and loved ones - into the picture.
Granted it's possible to imagine a much more agile approval process than the one we're lumbered with today. We may not have got the balance right between suppressing scams and approving treatments for people who otherwise have little hope. But the need to hold scammers down - and, perhaps even more so, ego-tripping quacks who have convinced themselves they're acting honestly - is real.
"First, do no harm" has been with us almost 2500 years, and with good reason.
Let's suppose in the base case - experimental treatments are largely suppressed and difficult to access - the odds are 10:1. That's a 10% chance of significantly prolonged survival, against 90% ineffective. And some of those "ineffective", maybe ten or twenty percent, will be actively harmful: shorter survival or a nastier death.
Unchecked, though, scammers will proliferate, and the odds get worse. Because incurable illnesses are, relatively speaking, very common compared to 10% shots at curing them. (If the reverse were true, we'd have eliminated many more of them with a shotgun approach). So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
And that's before we even factor money - and financial harm not just to the patient but to their family and loved ones - into the picture.
Granted it's possible to imagine a much more agile approval process than the one we're lumbered with today. We may not have got the balance right between suppressing scams and approving treatments for people who otherwise have little hope. But the need to hold scammers down - and, perhaps even more so, ego-tripping quacks who have convinced themselves they're acting honestly - is real.
"First, do no harm" has been with us almost 2500 years, and with good reason.
> And that's before we even factor money - and financial harm not just to the patient but to their family and loved ones - into the picture.
This can't be a serious argument when the ordinary medical establishment is the thing wiping out the bank accounts of anyone who gets seriously sick, regardless of whether or not it cures them.
If people are facing death and they have money, they're going to throw the money at attempts to not die, one way or the other.
> So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
But in this case the 10-20% harmful outcomes are in the nature of "you still died but maybe a little bit sooner" whereas the 1% effective outcomes are that you would have died and instead you didn't and lived another 50 years. If I have two months to live and there's a button I can press that has a 99% chance of making it one month and a 1% chance of making it 50 years, I'm smashing that button with no regrets.
You're also assuming we have no mechanism for detecting scams. But we do. Professionals go to school to learn science and that allows them to detect bullshit. If a substance is supposed to work against cancer by inhibiting cell growth and it's the sort of thing that could plausibly do that, it might not be a cure for cancer but it might be worth the attempt if you're going to die anyway. If a substance is supposed to work against cancer by mechanism of the astrology of Capricorn, that's a load of bullocks. So then the patient can ask a scientist they trust if the thing has any plausible mechanism of action before they waste their time or money on it.
Some of them may still be fools, but not all of them. Especially when the ones who aren't fools are the ones who are more likely to not die, which is the sort of thing otherwise-apathetic people tend to care about.
Moreover, in general "we have to kill some diligent people to keep some idiots from wasting their money" is not a sympathetic argument.
This can't be a serious argument when the ordinary medical establishment is the thing wiping out the bank accounts of anyone who gets seriously sick, regardless of whether or not it cures them.
If people are facing death and they have money, they're going to throw the money at attempts to not die, one way or the other.
> So now you're looking at 1% effective outcomes vs 10-20% harmful outcomes.
But in this case the 10-20% harmful outcomes are in the nature of "you still died but maybe a little bit sooner" whereas the 1% effective outcomes are that you would have died and instead you didn't and lived another 50 years. If I have two months to live and there's a button I can press that has a 99% chance of making it one month and a 1% chance of making it 50 years, I'm smashing that button with no regrets.
You're also assuming we have no mechanism for detecting scams. But we do. Professionals go to school to learn science and that allows them to detect bullshit. If a substance is supposed to work against cancer by inhibiting cell growth and it's the sort of thing that could plausibly do that, it might not be a cure for cancer but it might be worth the attempt if you're going to die anyway. If a substance is supposed to work against cancer by mechanism of the astrology of Capricorn, that's a load of bullocks. So then the patient can ask a scientist they trust if the thing has any plausible mechanism of action before they waste their time or money on it.
Some of them may still be fools, but not all of them. Especially when the ones who aren't fools are the ones who are more likely to not die, which is the sort of thing otherwise-apathetic people tend to care about.
Moreover, in general "we have to kill some diligent people to keep some idiots from wasting their money" is not a sympathetic argument.
> But if people can't choose for themselves then 100% of the time they die.
This is only true for a certain set of cases, and in those cases people generally can choose for themselves.
This is only true for a certain set of cases, and in those cases people generally can choose for themselves.
That's what right to try is. There are people who believe that should not be the case.
But the same logic also works for anything non-fatal as long as the proposed treatment is also non-fatal. If you want to try something and it probably won't work but it also probably won't cause permanent damage, there is nobody who should stop you from finding out what happens for yourself.
But the same logic also works for anything non-fatal as long as the proposed treatment is also non-fatal. If you want to try something and it probably won't work but it also probably won't cause permanent damage, there is nobody who should stop you from finding out what happens for yourself.
And in general nobody will stop you doing stuff to yourself.
The problem comes when these things are advertised or otherwise promoted. Ideas don't exist in a vacuum, they can become cultural parasites for all sorts of reasons, and even if they don't begin as a scam, there are always a bunch of get-rich-quickers waiting in the wings to sell, say, sheep dewormer to people with a respiratory virus.
The problem comes when these things are advertised or otherwise promoted. Ideas don't exist in a vacuum, they can become cultural parasites for all sorts of reasons, and even if they don't begin as a scam, there are always a bunch of get-rich-quickers waiting in the wings to sell, say, sheep dewormer to people with a respiratory virus.
> And in general nobody will stop you doing stuff to yourself.
The relevant doing stuff to yourself here is that you want to take some particular drug. Unless you're a competent chemist with the relevant equipment, that implies that somebody would have to be able to sell it to you in order for you be able to do it.
Also, what happens if the thing you want to do to yourself is to take MDMA?
The relevant doing stuff to yourself here is that you want to take some particular drug. Unless you're a competent chemist with the relevant equipment, that implies that somebody would have to be able to sell it to you in order for you be able to do it.
Also, what happens if the thing you want to do to yourself is to take MDMA?
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For this reason I have mixed feelings concerning Richard Scolyer’s glioblastoma treatment. On one hand it’s great that he has possibly found something that works and will in time become the new standard of care. At the same time it is disturbing that thousands of patients who are not renowned scientists have to die without a chance to try the same treatment.
It is disturbing. For some reason it’s not disturbing enough that we spend more to try and cure these diseases.
The Last Lecture was given almost 20 years ago. Pancreatic cancer is just as deadly today.
https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC
The Last Lecture was given almost 20 years ago. Pancreatic cancer is just as deadly today.
https://youtu.be/ji5_MqicxSo?si=bn6VBPaWraUfO-zC
You make a good point. Could there be a case for new ethical considerations to be made. The issue is patients are very vulnerable and no one really knows how bad the downside may be. A prolonged agonising or disabling death can be far worse.
> How many people die every year because we don't dare risk any deaths from uncertain treatments like these? Sure, they aren't ever going to be perfect, but- what's the net?
The trials exist. Getting patients enrolled in the trials is the biggest problem. Navigating the bureaucracy is a huge problem ("Please be dying, but not too quickly, part 1: a clinical trial story" see: https://bessstillman.substack.com/p/please-be-dying-but-not-...).
Even worse--we know the net to this stuff. It's negative and large.
We just went through this. Desperate people are stupid. Look at all the snake oil about Covid cures before the vaccines and how much damage that snake oil did.
And it's worse than that. It encourages ethical problems among the doctors themselves. You're sure your treatment will work it just needs a couple more patients. What will you do to get those patients?
Finally, if you throw the system open, the people playing by the rules will get drowned by those not. Bad money drives out good and all that.
The system as we have it certainly isn't ideal, but throwing things open would be much, much worse.
The trials exist. Getting patients enrolled in the trials is the biggest problem. Navigating the bureaucracy is a huge problem ("Please be dying, but not too quickly, part 1: a clinical trial story" see: https://bessstillman.substack.com/p/please-be-dying-but-not-...).
Even worse--we know the net to this stuff. It's negative and large.
We just went through this. Desperate people are stupid. Look at all the snake oil about Covid cures before the vaccines and how much damage that snake oil did.
And it's worse than that. It encourages ethical problems among the doctors themselves. You're sure your treatment will work it just needs a couple more patients. What will you do to get those patients?
Finally, if you throw the system open, the people playing by the rules will get drowned by those not. Bad money drives out good and all that.
The system as we have it certainly isn't ideal, but throwing things open would be much, much worse.
Very much this.
Experiments regularly take significant risks with peoples lives in the US, it’s far from 0. The barriers are surprisingly low, but come from a history of terrible experiments on the uninformed. People blame the FDA, but lawsuits are also considered a significant risk.
This rather famously killed ~100 men in the US and ended in 1972 long after effective treatments where available. https://en.wikipedia.org/wiki/Tuskegee_Syphilis_Study
But ethical violations are common, here’s one example where a whistleblower raised concerns in 2016 but it continued until Nov 2018 when funding ran out: https://www.kpbs.org/news/health/2021/02/12/new-details-unet...
This rather famously killed ~100 men in the US and ended in 1972 long after effective treatments where available. https://en.wikipedia.org/wiki/Tuskegee_Syphilis_Study
But ethical violations are common, here’s one example where a whistleblower raised concerns in 2016 but it continued until Nov 2018 when funding ran out: https://www.kpbs.org/news/health/2021/02/12/new-details-unet...
I think I’ve been hearing this argument for the last 40 years. How many miracle cures have we missed? None
If you really want to cure cancer, and other diseases like ALS, etc, invest the money and resources necessary to do it.
If you really want to cure cancer, and other diseases like ALS, etc, invest the money and resources necessary to do it.
How many died waiting for approval of cures we did find?
How many have died because we didn’t care enough to try harder to cure these terrible diseases. Tens of millions!
If you have a disease and want to find clinical trials for unapproved drugs, they are available.
https://clinicaltrials.gov/
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
If you have a disease and want to find clinical trials for unapproved drugs, they are available.
https://clinicaltrials.gov/
https://clinicaltrials.gov/study/NCT05855200?locStr=New%20Yo...
Far less than if we didn't have a proper system in place. We literally have miracle cures for things like measles, polio, and small pox yet people are far too stupid to take them. You think just letting people try whatever they want on people in a desperate situation is going to lead to good things?
> The patient, who is also an expert virologist, anticipating that the recurrent tumour would be of TNBC phenotype for which therapies of only limited efficacies exist, informed her oncologists that she was going to treat this tumour by the i.t. administration of viruses similar to oncolytic viruses (that were in clinical development for BC) before undergoing any other treatment.
Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.
Really smart to use the viral therapy before chemotherapy, since chemotherapy dampens the immune system, and the immune system probably promotes further tumor clearance once the tumors soften and are full of viruses.
Yes, the catch-22 mentioned in the article is that the clinical studies are done on late stage patients with usually at that point severely damaged immune system which of course wouldn’t produce desired effect especially if it is about using virus to cause flooding of the tumor with the immune response cells and not about virus directly attacking cancer cells. Also in the metastatic late stage one can imagine it isn’t really possible to inject each tumor.
This is a big simplification.
1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system.
2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness.
3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway.
4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors.
5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival.
This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.
1. The interaction between oncolytic virotherapy and host immunity is complex. Consider that oncolytic viruses are also targeted by the immune system.
2. Oncolytic viruses that directly destroy cancer cells may not depend on a host immune response at all for therapeutic effectiveness.
3. There are many common chemotherapy agents that enhance anti-tumor immunity. For example, 5FU is understood to enhance anti-tumor response and activate the p53 pathway.
4. Immunosuppressive chemotherapies can still enhance anti-tumor immunity by changing the tumor microenvironment. This is one of the principles behind combined chemo-immunotherapy regimes in treatment of solid tumors.
5. Some immune cells promote tumor growth and suppress anti-tumor immunity. Tumor associated myeloid cells are one example of an immune cell suppressed by chemotherapy that promote tumor survival.
This is just scratching the surface of some of the complexities here. In general, cancer and cancer treatment are incredibly complex with massive variation not just between types of cancer but within individual cancers themselves. Oncology does not lend itself to simplistic thinking.
I agree that it's a simplified explanation. However, in your first point you are making my point. An oncolytic virus can potentially give you a double whammy since even if the virus isn't able to kill a cancer cell, it might be able to recruit a local immune response and polarize cells from type 2 to type 1 immune response.
There are always exceptions to everything in biology, but the general mechanism of most chemotherapy drugs is that they preferentially kill or stall rapidly growing cells. That's why hair often falls out and you get skin issues. My point is that a successful immune response often involves rapid division of immune cell populations as well, which is dampened by chemo. You are also ineligible for many clinical trials if your blood cell counts get below a certain level.
Yes DNA-damaging chemotherapy drugs can induce p53, but many cancers inhibit p53 anyway. I'm not sure you would want to trade a general induction in p53 for losing a huge portion of your overall T-cell count right before injecting yourself with an oncolytic virus (depending on the tumor type).
You raise a number of good points, and there are a lot of subtleties including regulatory T-cells, which you mentioned. However, if you have the expertise and the means to design a custom treatment/regimen for yourself, I think that you can potentially do a lot better than just going through the meat-grinder of clinical oncology where the first line treatments are years behind cutting edge academic work. This paper supports this idea. I am not recommending that everyone who has cancer forgoes chemotherapy in favor of trying something risky, but as you said every individual case is different and it should be your decision whether you want to try a high-risk high-reward strategy or whether you want to go through multiple rounds of non-curative treatments which only slow down the inevitable and gradually sap away your strength and immune function. Especially if you have enough expertise in a relevant subject matter.
For example, my mother was diagnosed with stage 4 of a rare HPV+ squamous cell cancer. She was an expert on co-stimulation and immune tolerance, since she that is what she studied in the lab (https://tts.org/74-ixa/889-ixa-in-memoriam-agnes-marie-azimz... ). At times she was educating her doctor on co-stimulatory mechanisms, since he barely knew enough answer her questions and he would say the same types of things that you are saying: "it's complicated" "it might help clear cancer cells" etc..
There are a lot of customized treatments that she envisioned trying using her extensive expertise, and probably could have done so with the reagents in the lab or with her colleagues' help. Ultimately, she decided to trust the medical system but she did not respond to any chemotherapy. The one session which led to a reduction of tumor growth also led to a reduction in her blood cell counts (it was FOLFIRI), so the chemo had to be stopped. After that, she enrolled in an experimental cell therapy but it didn't work. Of course, the chances of it working are a lot less when her strength, general health, and immune function were already diminished.
It's one thing to talk about the complexities and the ethical risks of trying an experimental therapy, but when it happens to you or a loved one, the cost of failure is a lot higher and you might rethink your risk appetite. I am talking specifically about rare versions of tumors where the prognosis is poor.
In general, I don't even understand the point of making doctors go through all of the training they do, if they are forced to just follow the cookie cutter guidelines, which are influenced by the established drug companies.
There are always exceptions to everything in biology, but the general mechanism of most chemotherapy drugs is that they preferentially kill or stall rapidly growing cells. That's why hair often falls out and you get skin issues. My point is that a successful immune response often involves rapid division of immune cell populations as well, which is dampened by chemo. You are also ineligible for many clinical trials if your blood cell counts get below a certain level.
Yes DNA-damaging chemotherapy drugs can induce p53, but many cancers inhibit p53 anyway. I'm not sure you would want to trade a general induction in p53 for losing a huge portion of your overall T-cell count right before injecting yourself with an oncolytic virus (depending on the tumor type).
You raise a number of good points, and there are a lot of subtleties including regulatory T-cells, which you mentioned. However, if you have the expertise and the means to design a custom treatment/regimen for yourself, I think that you can potentially do a lot better than just going through the meat-grinder of clinical oncology where the first line treatments are years behind cutting edge academic work. This paper supports this idea. I am not recommending that everyone who has cancer forgoes chemotherapy in favor of trying something risky, but as you said every individual case is different and it should be your decision whether you want to try a high-risk high-reward strategy or whether you want to go through multiple rounds of non-curative treatments which only slow down the inevitable and gradually sap away your strength and immune function. Especially if you have enough expertise in a relevant subject matter.
For example, my mother was diagnosed with stage 4 of a rare HPV+ squamous cell cancer. She was an expert on co-stimulation and immune tolerance, since she that is what she studied in the lab (https://tts.org/74-ixa/889-ixa-in-memoriam-agnes-marie-azimz... ). At times she was educating her doctor on co-stimulatory mechanisms, since he barely knew enough answer her questions and he would say the same types of things that you are saying: "it's complicated" "it might help clear cancer cells" etc..
There are a lot of customized treatments that she envisioned trying using her extensive expertise, and probably could have done so with the reagents in the lab or with her colleagues' help. Ultimately, she decided to trust the medical system but she did not respond to any chemotherapy. The one session which led to a reduction of tumor growth also led to a reduction in her blood cell counts (it was FOLFIRI), so the chemo had to be stopped. After that, she enrolled in an experimental cell therapy but it didn't work. Of course, the chances of it working are a lot less when her strength, general health, and immune function were already diminished.
It's one thing to talk about the complexities and the ethical risks of trying an experimental therapy, but when it happens to you or a loved one, the cost of failure is a lot higher and you might rethink your risk appetite. I am talking specifically about rare versions of tumors where the prognosis is poor.
In general, I don't even understand the point of making doctors go through all of the training they do, if they are forced to just follow the cookie cutter guidelines, which are influenced by the established drug companies.
If you had to give a percent figure, what do you believe your mother's chances were of discovering a radical curative treatment for SCC and curing her own cancer?
I have no way to give a percent figure. 1%? But it doesn't matter, since there is a known 0% survival rate using the known treatments for SSC. In those cases it should be the patient's choice if they want a slow painful slide or if they want to roll the dice with something well considered but less well tested before the chemo wears them down to the point where their strength and immune system are worn down from multiple rounds of chemo. Effectively, the right to donate your body to science.
It’s interesting comparing the comments here to Twitter where there’s been a lot of discussion about the ethics of this (as in she shouldn’t have done this for some ethical reason that is never quite elucidated in detail, other than it’s wrong to do).
In contrast, many comments here are talking about the ethics of not having this approach more broadly available, which is fairly optimistic for Hacker News.
Or maybe it’s just that a subsection of bio-ethicists on Twitter have oddly shaped moral values.
In contrast, many comments here are talking about the ethics of not having this approach more broadly available, which is fairly optimistic for Hacker News.
Or maybe it’s just that a subsection of bio-ethicists on Twitter have oddly shaped moral values.
Twitter has the full gambit of ideologies, and the ethical models that those precommit a person to. It's amusing to watch the mental gymnastics required to come down against the common sense view that no one was negatively affected by her actions, and she personally benefited, and so it must be okay.
I think rational consequentialism is a common stance here on HN. e.g. I would be better off having access to this treatment (on my own terms of course), and other people having access to it would not negatively affect me, so I'm in favor.
I think rational consequentialism is a common stance here on HN. e.g. I would be better off having access to this treatment (on my own terms of course), and other people having access to it would not negatively affect me, so I'm in favor.
The most prominent bioethicist tweet, from @Strangviruslab, has over twice as many QT's as likes. It's among the biggest pile-ons I've ever seen on twitter.
This is particularly interesting to me because someone very close to me is in treatment for fairly advanced BC. While it might not be in time to help her, it’s exciting that someone is finally trying something very different than the normal approaches. Breast cancer treatment has continually advanced, but with only slow incremental progress, and where treatment is now still feels extremely primitive. In addition to having potentially life threatening or quality of life destroying side effects most normal treatments provide only moderate increase in lifespan unless you’re lucky enough to have early chemo clear it 100%. As I understand it hormone blocker therapy and the *mab drugs used in stage four usually lose effectiveness as the cancer mutates, such as to not depend on the presence of hormones to grow.
In a similar vein yesterday:
Four Thieves Vinegar Collective – Harm Reduction for the Living - https://news.ycombinator.com/item?id=41474080 - Sep 2024 (186 comments)
"Right to Repair–for Your Body. ... enabling access to medicines and medical technologies to those who need them but don’t have them"
DEFCON talk 2 days ago: https://www.youtube.com/watch?v=5rQklSmI_F0
Four Thieves Vinegar Collective – Harm Reduction for the Living - https://news.ycombinator.com/item?id=41474080 - Sep 2024 (186 comments)
"Right to Repair–for Your Body. ... enabling access to medicines and medical technologies to those who need them but don’t have them"
DEFCON talk 2 days ago: https://www.youtube.com/watch?v=5rQklSmI_F0
This is a fascinating area of research in general, but what’s notable here is that the researcher herself was afflicted with the tumors and self-administered these experimental treatments!
The really interesting part of this study (besides the obvious self-experimentation) is that she underwent subtype conversion from TN to HER2+ tumor and thus could use Trastuzumab.
The development of PD-L1 expression was also interesting.
Who was injecting the tumor? I'm squeamish enough I can't imagine being able to inject myself, let alone into a tumor...
I self-injected weekly for half a year for a much more mild and mundane reason (immunotherapy).
It sucked. Because I was doing it at home and not under observation, the dose schedule was way more conservative, so I'm not sure if it ended up saving any time at all despite the long drive to the clinic and the wait afterward. And stabbing yourself—even in the leg, as in my case—is not an easy thing to do. I thought it would get easier over time, and maybe it did a little, but there was a lot of variance and even towards the end some days it took me 10 minutes to psych myself up enough to do it. (Feeling monumentally foolish, but still not able to stick it in.)
Amusingly: after I switched to the conventional therapy of being injected by a nurse at a clinic, the nurse said she could never do it to herself. And she injects on the order of 100 patients per week!
Self-injecting into a breast... I can't even imagine. I guess the life-threatening nature, and not having an alternative, are powerful forces.
It sucked. Because I was doing it at home and not under observation, the dose schedule was way more conservative, so I'm not sure if it ended up saving any time at all despite the long drive to the clinic and the wait afterward. And stabbing yourself—even in the leg, as in my case—is not an easy thing to do. I thought it would get easier over time, and maybe it did a little, but there was a lot of variance and even towards the end some days it took me 10 minutes to psych myself up enough to do it. (Feeling monumentally foolish, but still not able to stick it in.)
Amusingly: after I switched to the conventional therapy of being injected by a nurse at a clinic, the nurse said she could never do it to herself. And she injects on the order of 100 patients per week!
Self-injecting into a breast... I can't even imagine. I guess the life-threatening nature, and not having an alternative, are powerful forces.
Cool, but how can we hack this?
With a Hackathon! And a couple of cohorts, just to be on the safe side.
Honestly, this is the first time I thought I was reading thriller novel, not a paper abstract.
Fascinating topic, I wonder where it would go. How does medic science bode with such "experiments"?
Really facinating. Using Virus to cure cancer.
Just like from I Am Legend movie.
``` The movie opens with a scene of Dr. Alice Krippin, who created the virus to cure cancer, discussing her work. Krippin states that 10,009 clinical trials were completed and all of the participants were successfully cured. However, it is later discovered that the virus is lethal.
A genetically modified measles virus kills most humans and turns some people into mutant creatures.
```
I hope it wont end up like `I Am Legend` movie. How long those research are being there , the movie script is a coincidence?
Just like from I Am Legend movie.
``` The movie opens with a scene of Dr. Alice Krippin, who created the virus to cure cancer, discussing her work. Krippin states that 10,009 clinical trials were completed and all of the participants were successfully cured. However, it is later discovered that the virus is lethal.
A genetically modified measles virus kills most humans and turns some people into mutant creatures.
```
I hope it wont end up like `I Am Legend` movie. How long those research are being there , the movie script is a coincidence?
This is the real world where science has redefined life expectancy and saves millions of lives a year, not a fictional will smith movie.
That's not the point, oncolytic viruses have been researched since the 1950s.
The fascinating thing is that this has been done in a self-experiment with viruses grown in her own lab.
The fascinating thing is that this has been done in a self-experiment with viruses grown in her own lab.
Institutional Review Board Statement
This is a case of self-experimentation. As such, it does not require ethics committee review [33,34,35]. The study was feasible only due to the unique situation in which the patient was also an expert virologist. The patient was fully aware of her illness as well as of available therapies, and as a scientist in the field of virology, she was aware of the potential of oncolytic virotherapy. After two recurrences of the same tumour, she wanted to try an innovative approach in a scientifically sound way. Her oncologists (the leading oncologists in Croatia for breast cancer) accepted to monitor the progress of the treatment, primarily with the aim of discontinuing the injections and intervening with conventional therapy if there were untoward effects or if the tumour progressed.