A cure for cancer: how to kill a killer(theguardian.com)
theguardian.com
A cure for cancer: how to kill a killer
https://www.theguardian.com/science/2018/nov/04/a-cure-for-cancer-how-to-kill-a-killer-revolutionary-immune-system-immunotherapy
95 comments
I am set to start treatment with Keytruda on Friday. I was fortunate that my tumor marker burden (TMB) was/is sufficiently high enough to get me into the clinical trial. I was equally fortunate that 1.) my oncologist is knowledgeable about all of these cutting edge therapies and 2.) my insurance will actually cover the cost.
Without the possibility of trying this my options would probably be dying slowly over the next couple of years or doing a very risky surgery that involves opening up my abdomen, cutting out as much of the disease as they can see and flooding the cavity with broad spectrum chemo (HIPEC.) Obviously, immunotherapy is much more palatable as the chemo was not pleasant.
Overall I am hopeful. I guess I don't really have a reason to post any of this, other than it helps to get it out there, so please excuse my rambling! And thanks for reading.
Without the possibility of trying this my options would probably be dying slowly over the next couple of years or doing a very risky surgery that involves opening up my abdomen, cutting out as much of the disease as they can see and flooding the cavity with broad spectrum chemo (HIPEC.) Obviously, immunotherapy is much more palatable as the chemo was not pleasant.
Overall I am hopeful. I guess I don't really have a reason to post any of this, other than it helps to get it out there, so please excuse my rambling! And thanks for reading.
My FIL has/had multiple melanoma. One of the tricks for him is his support group. They swap treatment research, good local doctors, emotional support, and when things get bad, they help out in the hospital with nurses, food-runs, etc. Please consider joining a support group. Some are better than others, so feel free to try more than one out and see which one works for you.
Oh, and Fuck Cancer.
Oh, and Fuck Cancer.
Thank you for sharing. All the best for your treatment. :)
Godspeed
> I guess I don't really have a reason to post any of this, other than it helps to get it out there
I know that feeling well. Best of luck to you.
I know that feeling well. Best of luck to you.
Very inspiring indeed. If I live long enough, I'll have lived through a period where most things that killed off my grand parents generation are in principle possible to treat. My impression is that if I manage another 20 years or so, my risk profile for dying of things that currently very common causes of death (i.e. likely to kill me), will have changed completely. That's long enough for me but may not be long enough for people I care about.
I'll spare you the cliches; we all know people that died of something (or are dying of something). But it is very heartbreaking to know about people suffering right now when the cure for what is killing them might be just around the corner.
I'll spare you the cliches; we all know people that died of something (or are dying of something). But it is very heartbreaking to know about people suffering right now when the cure for what is killing them might be just around the corner.
@doctoring - I am at the early stages of a start-up focusing on oncology. Would love to interview you if you have time. Feel free to reach out to me here: https://www.linkedin.com/in/gunnr/
In aother article pointed by the Guardian, I read :
>> Schmid said: “Immune therapy on top of standard chemotherapy prolonged survival by ten months
Since, I guess, patient are interested by "being cured", how should I interpret those ten additional months? Of course, I understand the statistic behind it, but I' d like to know if it translates to something meaningful for the life of the patient. For example, if I had a ten month increase in my life, considering that it could mean live 10 month more with pain, false hopes, etc., then I wouldn't feel that the situation has improved meaningfully (of course I don't have cancer and therefore I may miss some obvious benefits). OTOH, if that increase means that the chance of long time remission also increase, then, that's a whole different situation...
>> Schmid said: “Immune therapy on top of standard chemotherapy prolonged survival by ten months
Since, I guess, patient are interested by "being cured", how should I interpret those ten additional months? Of course, I understand the statistic behind it, but I' d like to know if it translates to something meaningful for the life of the patient. For example, if I had a ten month increase in my life, considering that it could mean live 10 month more with pain, false hopes, etc., then I wouldn't feel that the situation has improved meaningfully (of course I don't have cancer and therefore I may miss some obvious benefits). OTOH, if that increase means that the chance of long time remission also increase, then, that's a whole different situation...
quality vs quantity is a very real qualification you need to think about. typically doctors are more concerned with quantity -- ie they have to "do something" if they can
In my experience as a cancer survivor, it's all about "staying in the game". Medicine doesn't change as fast as software, but extra months means a chance to access new treatment options as they emerge.
I'm another cancer survivor. My understanding is that you don't take this treatment with the goal of surviving extra 10 month. You take in in the hope to be cured, because they say there is a chance, however slim. So the rational choice for me would be: take the treatment, and if in a couple of months it proves ineffective, take euthanasia (if it's legally possible, which is the case where I live - though probably there are still some unfortunate legal caveats),
Just hanging around longer would serve no purpose except increasing the pain for my family. (That's my personal view only, not intended as a template for anybody else)
But for all those who "stay in the game", only a proportion get to survive, and some of those who do not give up meaningful quality of life for 2-3 months more time.
Situations are complex and outcomes are highly varied. One size does not fit all.
Situations are complex and outcomes are highly varied. One size does not fit all.
Sometimes an extra 10 months means seeing your child graduate college / get married / have your first grandchild.
Which is really more for them than for you. When you're dead, it won't matter to you that you saw those things, but it might matter to your child for the rest of his/her life.
It is not about seeing these things as an uninvolved observer. It is about receiving a share of an important moment that is meaningful on a personal level. And these are some of the things that make life worth living.
We do not know if there is a meaning to life. But on a human level we are connected through social connections and these people who are connected to us can give life a meaning on some level.
I also disagree that death makes you no longer care. Yes, you as a person supported by a mortal body will no longer feel anything. But the concepts that made up your personality and the actions you took while being alive will still influence the events in the world. You cannot react any more, but most people at least define a written will for the time after they are dead. Just take the nobel prize. It is based on a will that wants to shape the world for the better long after the body of Alfred Nobel has died. The nobel prize is still going strong.
We do not know if there is a meaning to life. But on a human level we are connected through social connections and these people who are connected to us can give life a meaning on some level.
I also disagree that death makes you no longer care. Yes, you as a person supported by a mortal body will no longer feel anything. But the concepts that made up your personality and the actions you took while being alive will still influence the events in the world. You cannot react any more, but most people at least define a written will for the time after they are dead. Just take the nobel prize. It is based on a will that wants to shape the world for the better long after the body of Alfred Nobel has died. The nobel prize is still going strong.
Remember: "today is the first day of the rest of your life".
The fact that the rest of one's life is "short" compared to someone else's does not mean that it's less subjectively meaningful.
The fact that the rest of one's life is "short" compared to someone else's does not mean that it's less subjectively meaningful.
Yeah, but when your child dies, it won't matter to them anymore either.
You can't bet just 50% on nihilism. Either go all in or acknowledge that people want to have as many positive experiences as they can, no matter how much time they have left.
You can't bet just 50% on nihilism. Either go all in or acknowledge that people want to have as many positive experiences as they can, no matter how much time they have left.
Most people don’t want to die, surprisingly.
Since the final solution for cancer doesn't exists (yet), every improvement is better than nothing. We will all die. So the question is: how long will a person live. Prolonged life means some "extra days" for cancer patients...
Life is all about how we spend the moments before death? Those 10 months are more opportunity. They needn't be a 'situation' response; they can be just more living.
Could that tech of re-engineering T-cells be a step to cure psoriasis? AFAIK psoriasis is caused by T-cells erroneously targeted to kill epidermis.
With the current CAR-T technology, you’re “turning on” the T-cell so it attacks certain cell types. You only need a few of those cells as they can multiply within the body.
What you’re talking about is the opposite, turning the T cell “off”. You’d also need to do that to every T cell or alternatively, destroy every T cell and restart with a batch of new cells.
Very different problems.
What you’re talking about is the opposite, turning the T cell “off”. You’d also need to do that to every T cell or alternatively, destroy every T cell and restart with a batch of new cells.
Very different problems.
Or program the T-cells to attack mesenchymal cells that are producing the defective ones. I'd wager that the process would still be much more difficult than targeting cancerous cells, and certainly be very complicated.
But, there's hope for other diseases, though the article is focused on cancer:
> Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.
But, there's hope for other diseases, though the article is focused on cancer:
> Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.
I have an idea for curing psoriasis. It sounds really ridiculous but seeing eating local honey cured my pollen allergies I think it could be worth a try.
I am curious about your idea, do you mean that it would be enough to eat honey to cure psoriasis, or is it something else?
Thanks!
I’m proposing eating that which your allergies are attacking. Your skin.
I guess you’d need to design some kind of exfoliator to get enough skin. I told you it sounds ridiculous.
I guess you’d need to design some kind of exfoliator to get enough skin. I told you it sounds ridiculous.
It may sound ridiculous but it is an interesting idea.
Normally an adaptive immune reaction has two phases, one where T-cells are aggressively deployed and another where it slows down (resolution phase).
Many chronic diseases involve some kind of "immune vicious circle" with no resolution phase.
T-cells are "educated" mainly in the thymus, if it was possible to alter the education mechanism, we could better manage auto-immune diseases.
At least your suggestion is yummy food for thought, thanks!
And for good reason
Thank you for such a detailed answer. I'm not an expert by any means, have just a random question. Is it possible to transport markers from people who have them to those who don't? I have zero clue what I'm talking about, but this is the first thought came to my mind and I was too curious not to ask.
As far as I know, 'markers' reflect metabolic/functional attributes in malignant cells. The question about any type of cancer is wether you can target the malignant cells somewhat exclusively or not. Does the cancer retains healthy features as pathways to cell arrest or apoptosis? Is its metabolism so rapid, to make it's growth distinct over a certain time frame? Is its growth influenced by external signalling? Can the immune system find the malignant cells? The problem really is that cancer is often very heterogeneous, which means a targeted treatment might not kill all of it, leading to evolutionary drive and resistant reoccurrence. The more control mechanisms lost, the wilder the mutations. So worst case, you got cells that behave nothing like a normal cells, but generally can't be distinguished/targeted on a cellular level AND are not localized lesions anymore.
So, no, I don't think so. To theoretically transfer a distinct marker to all cancer cells, you'd need a distinct target in the first place.
So, no, I don't think so. To theoretically transfer a distinct marker to all cancer cells, you'd need a distinct target in the first place.
Do you think there's a boon in research that may lead to larger populations responding to immunotherapies ? And if so, should we change protocols to sustain people with incurable tumors just long enough to get a potential treatment ?
Thank you so much for doing this.
Assuming anyone can afford these therapies.
Is there any evidence that as these techniques are refined we can find ways to apply them to more people OR is it just a matter of your cancer having mutation X or not, no way around it. I’m thinking about Judy Perkins and how her success with stage 4 breast cancer.
People seem to be disturbed by the indiscriminate nature of this cure. The immune system, unleashed, will target not only cancer cells but healthy ones as well. If this feels somehow aesthetically displeasing to you, ask yourself whether it feels more or less clumsy to shoot radiation in your tumor's general direction and literally poison yourself. Immunotherapy seems positively elegant in comparison.
Um, actually, radiation is MUCH better than most of the chemical options unless you are one of the very fortunate few that has a particular receptor than can be targeted.
Radiation has gotten extremely good at being far more targeted. The doctors actually model the absorption curves and let computers target the specific areas to make sure that the specific area gets the necessary dose while keeping the dose down in the surrounding tissue. If you can do radiation, it is by far the best option nowadays. Sadly, you can't always use it--sometime surrounding tissue is too sensitive to radiation (intestines) and sometimes things are simply too large.
Chemotherapy, though, just really, really, sucks. Almost anything is better.
Radiation has gotten extremely good at being far more targeted. The doctors actually model the absorption curves and let computers target the specific areas to make sure that the specific area gets the necessary dose while keeping the dose down in the surrounding tissue. If you can do radiation, it is by far the best option nowadays. Sadly, you can't always use it--sometime surrounding tissue is too sensitive to radiation (intestines) and sometimes things are simply too large.
Chemotherapy, though, just really, really, sucks. Almost anything is better.
Yeah I hesitated at putting radiation therapy in there because I didn't know how targeted it was. Thanks for an informative response.
Slightly off-topic but one thing that I've always been honestly curious about is that literally billions of dollars are donated to cancer research each year...but then the practical results of the research are sold to oncology patients at bankrupting sums.
So my question is when we donate to cancer research, are we donating to public research or are we handing our money to a for-profit corporation. What is the path from donation to six figure cancer treatments? I would be very interested in how that works.
So my question is when we donate to cancer research, are we donating to public research or are we handing our money to a for-profit corporation. What is the path from donation to six figure cancer treatments? I would be very interested in how that works.
> the practical results of the research are sold to oncology patients at bankrupting sums.
In the US. [0]
[0] https://www.healthsystemtracker.org/chart-collection/how-do-...
In the US. [0]
[0] https://www.healthsystemtracker.org/chart-collection/how-do-...
The rest of the world can thank people in the US for spending rather large sums on certain treatments. In the UK the treatments are covered by the state at no cost to the patient, but it's only a limited set of available treatments which are considered cost effective. In the US there are plenty more options, if you can pay for it. People may decide to bankrupt themselves or sell their house for these treatments that could enable them to survive or not, but either way they are contributing to real world data that informs the rest of the world of the efficiency and cost effectiveness of a particular treatment.
The research part of research and development is primarily done by publicly funded researchers. The development part is primarily done by private ones, who expend huge sums of money on trying many different candidate therapies and shepherding them through safety and efficacy trials, which almost all of them fail, at huge expense.
If we want to increase the rate of return on investment the big, easy win would be dropping the efficacy test. If we want to reform the system of funding altogether buy out patents for their market value or give massive prizes and then have the drugs freely available for anyone to manufacture.
If we want to increase the rate of return on investment the big, easy win would be dropping the efficacy test. If we want to reform the system of funding altogether buy out patents for their market value or give massive prizes and then have the drugs freely available for anyone to manufacture.
Donations likely contribute to the body of knowledge about cancer. Then someone takes that and develops a new drug, charging a high price along with it.
An interesting approach is the cystic fibrosis association in the US that directly invested in a new CF drug. They made a ton of money and rolled it back into research.
An interesting approach is the cystic fibrosis association in the US that directly invested in a new CF drug. They made a ton of money and rolled it back into research.
There's a lot of grants for cancer research coming from donation dollars. For the Leukemia and Lymphoma society, which I've contributed to numerous times, they fund early-stage research going on at academic institutions mostly, though trials and patients are also supported. A number of their early-stage funded research projects have advanced to official FDA trials.
The overall issue you're speaking of is the healthcare system in the US, which is not present in other countries where drugs and treatments may be present, albeit slightly delayed, for much cheaper. Some of the most expensive options are biologic drugs, which cost a lot but that's because they are more difficult to manufacture and are often tailored to the individual patient level.
Still, the US healthcare system is supporting the main engine of biotechnological research in the world. Look at Cambridge, MA and you will see huge brain drain and financial investment into pharma and biotech companies.
The overall issue you're speaking of is the healthcare system in the US, which is not present in other countries where drugs and treatments may be present, albeit slightly delayed, for much cheaper. Some of the most expensive options are biologic drugs, which cost a lot but that's because they are more difficult to manufacture and are often tailored to the individual patient level.
Still, the US healthcare system is supporting the main engine of biotechnological research in the world. Look at Cambridge, MA and you will see huge brain drain and financial investment into pharma and biotech companies.
For-profit companies actually fund more R&D than public research does (globally the biopharma industry spends $200B+ on R&D a year; NIH budget is $34B; not sure about other countries' public medical research budgets but doubt international public drug R&D approaches $200B tho i could be wrong).
Typically the way it works today is that an academic group, startup or big pharma company will have a "seed" of an idea for a drug. Some of the early drug discovery work happens in academia, some in startups, some at big pharma. But by the time that a potential drug enters preclinical development it is almost always owned by a for-profit company because they have the budget and resources for this work. At this stage fewer than 0.01%-5% of candidate drugs end up working and getting approved by FDA, and it costs tens or hundreds of millions to get a drug approved (and it can cost multiples of that if you include cost of failed drugs). So these companies take a tremendous amount of risk.
These days startups do most of the late stage discovery / early stage development work. They often take the drugs through the riskiest phases of development, generally up to Phase 1/2 or Phase 2 where effectiveness is first tested in humans. Phase 2 failure is the single largest driver of the cost of drug development. Phase 2 failure rates are as high as 60-70%, and it can cost $100M+ to get a drug to Phase 2.
In many cases a startup will try to sell their drug to big pharma after good Phase 2 data. At this point the risk is much lower (drugs have a better than 50% chance of getting approved), but they require significant funding to do the large Phase 3 studies needed for approval and to fund commercialization (can need 9 figures just for Phase 3 work and submission to FDA). So at this point it is a lower risk / lower return bet, but an expensive one, and big pharma companies are structured to take those bets.
However big pharma companies also spend a lot on early stage R&D. From looking at SEC filings, it seems roughly half of big pharma R&D is early stage and half late stage. The problem is that big pharma typically does not do well at early R&D. The return on investment in R&D at big pharma companies is approaching 0%.
Much of the high price of drugs is simply a function of the high risk and high cost of drug development. Very few drugs that pharma invests in actually become profitable drugs. So they try to milk all they can out of the few winners. It isn't the case that pharma's business model is buying fully derisked products from academia and then jacking up the price.
And while at some point publicly funded research could replace for-profit research, the reality today is that if we didnt have for-profit drug research then we would not have new drugs.
in 2017 the FDA approved 49 new drugs. None of those were owned by non-profits at approval (one was owned by a public-private JV). There is not enough non-profit money to take drugs through the development process to FDA approval
And when high prices do exist, in many cases it is because the drugs literally save lives. If you value a QALY at $50K / year (a common estimate), and your drug enables a child to live a full life who otherwise would have died at age 2 due to a rare genetic disease, it doesn't seem absolutely crazy to charge $1M for that drug. The issue to me seems to be more 1) what happens if you pay $1M for a drug and it doesn't work or 2) what if the patient cannot afford to pay $1M upfront for the drug even if it is guaranteed to add 20 healthy years to your life.
Typically the way it works today is that an academic group, startup or big pharma company will have a "seed" of an idea for a drug. Some of the early drug discovery work happens in academia, some in startups, some at big pharma. But by the time that a potential drug enters preclinical development it is almost always owned by a for-profit company because they have the budget and resources for this work. At this stage fewer than 0.01%-5% of candidate drugs end up working and getting approved by FDA, and it costs tens or hundreds of millions to get a drug approved (and it can cost multiples of that if you include cost of failed drugs). So these companies take a tremendous amount of risk.
These days startups do most of the late stage discovery / early stage development work. They often take the drugs through the riskiest phases of development, generally up to Phase 1/2 or Phase 2 where effectiveness is first tested in humans. Phase 2 failure is the single largest driver of the cost of drug development. Phase 2 failure rates are as high as 60-70%, and it can cost $100M+ to get a drug to Phase 2.
In many cases a startup will try to sell their drug to big pharma after good Phase 2 data. At this point the risk is much lower (drugs have a better than 50% chance of getting approved), but they require significant funding to do the large Phase 3 studies needed for approval and to fund commercialization (can need 9 figures just for Phase 3 work and submission to FDA). So at this point it is a lower risk / lower return bet, but an expensive one, and big pharma companies are structured to take those bets.
However big pharma companies also spend a lot on early stage R&D. From looking at SEC filings, it seems roughly half of big pharma R&D is early stage and half late stage. The problem is that big pharma typically does not do well at early R&D. The return on investment in R&D at big pharma companies is approaching 0%.
Much of the high price of drugs is simply a function of the high risk and high cost of drug development. Very few drugs that pharma invests in actually become profitable drugs. So they try to milk all they can out of the few winners. It isn't the case that pharma's business model is buying fully derisked products from academia and then jacking up the price.
And while at some point publicly funded research could replace for-profit research, the reality today is that if we didnt have for-profit drug research then we would not have new drugs.
in 2017 the FDA approved 49 new drugs. None of those were owned by non-profits at approval (one was owned by a public-private JV). There is not enough non-profit money to take drugs through the development process to FDA approval
And when high prices do exist, in many cases it is because the drugs literally save lives. If you value a QALY at $50K / year (a common estimate), and your drug enables a child to live a full life who otherwise would have died at age 2 due to a rare genetic disease, it doesn't seem absolutely crazy to charge $1M for that drug. The issue to me seems to be more 1) what happens if you pay $1M for a drug and it doesn't work or 2) what if the patient cannot afford to pay $1M upfront for the drug even if it is guaranteed to add 20 healthy years to your life.
Thanks for the informative insight.
> if we didnt have for-profit drug research then we would not have new drugs.
I don't think that follows. If we didn't have for-profit drug research, we would have less volume of safety and efficacy testing and data on drugs, but we would still 'have' the drugs.
I think drug testing reform must be part of the solution. Bringing a drug to market is too expensive.
> if we didnt have for-profit drug research then we would not have new drugs.
I don't think that follows. If we didn't have for-profit drug research, we would have less volume of safety and efficacy testing and data on drugs, but we would still 'have' the drugs.
I think drug testing reform must be part of the solution. Bringing a drug to market is too expensive.
A more fully accurate version of my statement would be we wouldn't have "FDA approved" drugs, but I dont think it's accurate to say we would still have the drugs without for profit research. Many (most?) approved drugs are discovered and developed entirely within for-profit institutions. And much of the technology licensed from academia are just assays (not chemical matter) which are used by pharma companies to screen libraries of drug-like molecules, which they must then optimize before they can be "drugs". Sometimes companies license drug like compounds straight from academia but it is rare that these compounds are fully optimized for human use -- sometimes they are very rudimentary and wouldn't be suitable for human use without significant optimization -- and they aren't really yet "drugs"
Pharma companies don't just run clinical studies. They do a massive amount of discovery work and preclinical development, probably on the order of $100B worth / year
I do agree that drug testing reform can play an important role in lowering the cost of drug development. Things like not requiring cardiovascular outcomes studies for diabetes meds would be a great start, and providing clearer guidance for development of complex generics. However i dont know what else might be done that wouldnt compromise the quality of approved drugs, a lot of the difficulty is just our limited ability to directly study human biology
Pharma companies don't just run clinical studies. They do a massive amount of discovery work and preclinical development, probably on the order of $100B worth / year
I do agree that drug testing reform can play an important role in lowering the cost of drug development. Things like not requiring cardiovascular outcomes studies for diabetes meds would be a great start, and providing clearer guidance for development of complex generics. However i dont know what else might be done that wouldnt compromise the quality of approved drugs, a lot of the difficulty is just our limited ability to directly study human biology
Not directly connected to the article, but the 40% chance of getting diagnosed with cancer in my lifetime really sets of my anxiety...
If you live long enough you will eventually get some kind of cancer. This is inevitable as DNA damage accumulates. Chances are something else will kill you first, but detailed autopsies of older people frequently turn up small, slow-growing cancer tumors.
It's why at a certain age with Prostate cancer "watchful waiting" is often preferable to invasive procedures. In some cases it will be so slow growing you're likely to die of something else first.
You have 100% chance of dying of something.
The article follows the standard convention of newspapers to hide any qualifiers in the last few paragraphs, in particular the second to last paragraph starts:
> Hype can be dangerous, just as false hope can be cruel.
I would therefore suggest reading the last two paragraphs carefully.
> Hype can be dangerous, just as false hope can be cruel.
I would therefore suggest reading the last two paragraphs carefully.
They aren't hidden, they are just at the end of the article. To me this seems like fairly honest reporting, as opposed to ommitting this info entirely.
The immune system is so complex, we can't even solve food allergies. We're only scratching the surface, although I am hopeful for the future.
I'm worried about these treatments for people with autoimmune diseases. One, they might be on immunosuppressants, two, immune activation can then kill you through the autoimmune disease.
I have ulcerative colitis and am on immunosuppressants. So I'm more likely to get cancer and can't get that treatment.
I have ulcerative colitis and am on immunosuppressants. So I'm more likely to get cancer and can't get that treatment.
At our hospital we routinely use many of these therapies even in patients with a variety of autoimmune conditions. In about a third of patients, they'll have an exacerbation of their underlying autoimmune condition, which fortunately only rarely necessitates cessation of the immunotherapy.
One of several studies we reference when we treat these patients: https://www.ncbi.nlm.nih.gov/pubmed?term=27687304
What's interesting (and increasingly being studied) is the higher risk of developing an autoimmune condition after treatment with some of these immunotherapies. The absolute risk doesn't seem to be huge, but it's an interesting window into how these conditions might develop in the first place.
One of several studies we reference when we treat these patients: https://www.ncbi.nlm.nih.gov/pubmed?term=27687304
What's interesting (and increasingly being studied) is the higher risk of developing an autoimmune condition after treatment with some of these immunotherapies. The absolute risk doesn't seem to be huge, but it's an interesting window into how these conditions might develop in the first place.
That's good to hear. Would you stop, say Humira before treatment?
One would imagine they will not be used in these cases
What the article unfortunately not explains: as far as I understand the medication suppresses ways the immune system can identify healthy/own cells of the body. If that is suppressed I'd expect more severe side effects, up to death, no less. Why isn't this the case? Imho it could work only if cancerous cells are more affected than healthy ones (like they are more affected by cytostatic drugs because they divide faster). Can anyone chime in with an explanation?
Some additional info here - https://www.quora.com/How-does-PD-L1-checkpoint-inhibition-s...
Pardon my naïveté. Has a honey-pot strategy been tried for Cancer? Like maybe we can't kill it but we can lure it to develop in a very localized place, like a cyst growing on the back of your hand or something, and then we remove the cyst.
When cancer metastasizes, that means newly divided cells from the tumor have penetrated the blood stream or lymph system, and are circulating around the body. They will accumulate and grow anywhere that they happen upon if the conditions for growth are favorable.
The primary tumor isn't packing up and migrating, it is rooted in place like a tree. A cancer cell circulating through your body doesn't seek to get to the lung, it just might happen to end up there and it might grow well there and form a new tumor, like an acorn falling off a tree. Some acorns will fall into rich soil, some will fall on pavement or get eaten. You can't coax acorns to fall squarely into your bucket, and even if you did you still have the tree to deal with.
The primary tumor isn't packing up and migrating, it is rooted in place like a tree. A cancer cell circulating through your body doesn't seek to get to the lung, it just might happen to end up there and it might grow well there and form a new tumor, like an acorn falling off a tree. Some acorns will fall into rich soil, some will fall on pavement or get eaten. You can't coax acorns to fall squarely into your bucket, and even if you did you still have the tree to deal with.
Just as naive as you about this, but why would cancer developing in one place mean that it can't develop somewhere else?
Ok, following with the totally naive speculation. What if it were not a place, but a specific environmental factor or a specific trait? Cancers mutate quickly, and resources are limited, so cells that are more successful might starve those which lag behind, as it happens in animal populations. And once the cancer has "fallen into the trap" of specializing for something, that something could be targeted, or the favouring environmental conditions removed.
This is the clonal evolution model of cancer, and is how many solid tumors are comprised and treated. The danger is that the selective advantage for the cancer cell is often by masking itself as a healthy cell to the immune system, which complicates treatments but this interaction can still be targeted (see PD-1).
Yes, the idle speculation about a "honeypot" method was of artificially encouraging the cancer to evolve in a certain direction, even boosting its growth, until it has reliably mutated in a way that makes it susceptible to some other intervention, like being starved or targeted by some particular marker.
There's not actually one disease called "cancer". Cancer is just the catch-all term for a large set of disorders where cells grow at an uncontrolled rate. Such a disorder can develop in different ways, for different reasons, in different cells, at different times, etc.
Honeypots only work when there is consistent attack pattern to detect, and a means to mitigate that attack. But with cancer, getting a tumor to grow in one kind of cell will not prevent a different kind of cancer from developing in a different kind of cell.
Honeypots only work when there is consistent attack pattern to detect, and a means to mitigate that attack. But with cancer, getting a tumor to grow in one kind of cell will not prevent a different kind of cancer from developing in a different kind of cell.
I am honestly curious. What exactly is the root cause of cancer? The article talks about cancerous cells tricking the immune system, but this trickery is the result of something else. Immune system, in a healthy body, eliminates cancer cells continuosly. What enables some cancer cells in some humans to fool the immune system and multiply maliciously?
We can "manage" cancer without understanding the root cause. We cannot cure it.
We can "manage" cancer without understanding the root cause. We cannot cure it.
Just evolution whispering “kill, consume, multiply, conquer” to the cells in your body in the normal way that evolution does. It's pretty common for small mutations to occur in your cells from time to time. Cancer requires several mutations to line up in ways that allows cells to start multiplying without constraint - evading normal growth controls and apoptosis and the immune system and such. The cells where the mutations don't align and which start multiplying with everything else you never even notice.
> Cancer requires several mutations to line up in ways that allows cells to start multiplying without constraint - evading normal growth controls and apoptosis and the immune system and such.
In that case, either we are engineered badly (genetic) or there are factors that cause cells to go rogue (epigenetic). We still need to find the root cause.
I have a hard time believing there are faults in the way we are designed.
In that case, either we are engineered badly (genetic) or there are factors that cause cells to go rogue (epigenetic). We still need to find the root cause.
I have a hard time believing there are faults in the way we are designed.
It's not that there's a fault in evolution's design so much as that evolution doesn't really care that much that people die of cancer. Whether or not it could be possible to create a non-senescent humanoid species by evolution evolution has a fixed budget of complexity it can work with given germline mutation rates and the selective pressure our species is under. And reducing germline mutation would mean we would evolve more slowly in the face of new selective pressures like new diseases.
People are working on ways to end cancer. Aubrey de Grey has a plan[1] which, unlike his others for fighting aging, I think is totally crazy but hey at least someone is working on it. But its certainly not something that could evolve in nature.
[1]https://en.wikipedia.org/wiki/Strategies_for_Engineered_Negl...
People are working on ways to end cancer. Aubrey de Grey has a plan[1] which, unlike his others for fighting aging, I think is totally crazy but hey at least someone is working on it. But its certainly not something that could evolve in nature.
[1]https://en.wikipedia.org/wiki/Strategies_for_Engineered_Negl...
Reminds me of the suicide gland of some cephalopods with mating. It is one thing to starve to death while guarding their eggs constantly but an actual gland to kill them?
Likely a result of letting their niche be taken by descendants made them more adaptable than ones which lived until other constraints or more or less bad luck (cummulative fatality risks over time) killed them.
Likely a result of letting their niche be taken by descendants made them more adaptable than ones which lived until other constraints or more or less bad luck (cummulative fatality risks over time) killed them.
All higher living organisms are composed of cells. Each cell runs biological DNA-based programs. These programs are very different compared to programs on a computer (it's much more about biochemistry than electrical circuits). These programs are supposed to make cells perform their tasks correctly. But over time, the DNA can be affected by chemicals or faulty copy processes. The DNA sequence changes and the program "code" of the DNA is affected as well. The cells with altered DNA will behave slightly differently and in many cases nothing bad happens. But sometimes the changes affect functionality that is important to control the behaviour of the cell.
The thing is, a single cancer cell is not a problem. The problems really start, once the cancer cells creates a great number of copies of itself and disrupts the operations of the other normal cells.
What makes cancer tricky, is that cancer cells still are derived from normal cells and they might look too similar to normal cells so that it is difficult for the immune system to spot and kill them.
What is now the root cause? The root cause is errors in the DNA sequence that accumulate over time. This is a natural process. The cells have some DNA repair mechanisms, but they are not perfect. To fully cure cancer, you would need to correct all DNA sequence errors which is not practical. However, in practise, this is not what is needed. Instead, it suffices if the cancer cells are being killed. And our immune system is pretty good at this. But at some point, some cancer will have a faulty DNA seuence, with new program code, that helps it hide from the immune system and then we need the help of doctors to get rid of the cancer.
The thing is, a single cancer cell is not a problem. The problems really start, once the cancer cells creates a great number of copies of itself and disrupts the operations of the other normal cells.
What makes cancer tricky, is that cancer cells still are derived from normal cells and they might look too similar to normal cells so that it is difficult for the immune system to spot and kill them.
What is now the root cause? The root cause is errors in the DNA sequence that accumulate over time. This is a natural process. The cells have some DNA repair mechanisms, but they are not perfect. To fully cure cancer, you would need to correct all DNA sequence errors which is not practical. However, in practise, this is not what is needed. Instead, it suffices if the cancer cells are being killed. And our immune system is pretty good at this. But at some point, some cancer will have a faulty DNA seuence, with new program code, that helps it hide from the immune system and then we need the help of doctors to get rid of the cancer.
AIUI, it isn't really a single disease with a specific cause. It's more like, our body is composed of trillions of individual cells. Each cell is theoretically an independent life form capable of doing its own thing. They normally each have a program, encoded in their DNA, that keeps them operating in service of the overall organism of our body - replicating only when needed, dying when not needed, doing things useful to the body while they're alive, etc. There's various environmental factors, radiation and chemicals and such, constantly attacking that DNA. The DNA has self-repair mechanisms, plus the body's defense mechanisms to kill badly behaving cells, so most mutations are either repaired, ignored, or immediately fatal to the cell, kind of like changing a random character in your program.
Over all of those trillions of cells and dozens of years, once in a while, a particular cell gets just the right batch of random mutations that make it possible to stay alive while breaking free of its programming and acting as its own organism, independent of the body's plan. It may then proceed to reproduce on its own, potentially disrupting the body's functions and/or consuming all of its resources if it grows quickly enough.
So each individual cancer case is a uniquely evolved life form. There's a few common threads that many tend to share, but no telling how many each particular case may have. Thus, the broad brush approaches tend to be the most successful - surgery, chemotherapy, and radiation. More directed genetic approaches are tougher because of the uniqueness of each case.
Evolutionarily, it's a tricky balance. Too few mechanisms to keep all of your cells under control all the time, and your body dissolves into a mess of cancers too soon, like before you can reproduce. Too many mechanisms wastes resources, can potentially go haywire and damage your body themselves, like autoimmune diseases, or make it too hard for your body to evolve new and useful adaptations to the environment. We already have good enough controls that getting cancer before normal reproduction age is very rare. But now we're living a lot longer, much longer than our bodies are evolutionarily adapted to keep us alive for, so we see a lot more of these kinds of problems.
Over all of those trillions of cells and dozens of years, once in a while, a particular cell gets just the right batch of random mutations that make it possible to stay alive while breaking free of its programming and acting as its own organism, independent of the body's plan. It may then proceed to reproduce on its own, potentially disrupting the body's functions and/or consuming all of its resources if it grows quickly enough.
So each individual cancer case is a uniquely evolved life form. There's a few common threads that many tend to share, but no telling how many each particular case may have. Thus, the broad brush approaches tend to be the most successful - surgery, chemotherapy, and radiation. More directed genetic approaches are tougher because of the uniqueness of each case.
Evolutionarily, it's a tricky balance. Too few mechanisms to keep all of your cells under control all the time, and your body dissolves into a mess of cancers too soon, like before you can reproduce. Too many mechanisms wastes resources, can potentially go haywire and damage your body themselves, like autoimmune diseases, or make it too hard for your body to evolve new and useful adaptations to the environment. We already have good enough controls that getting cancer before normal reproduction age is very rare. But now we're living a lot longer, much longer than our bodies are evolutionarily adapted to keep us alive for, so we see a lot more of these kinds of problems.
I agree with most of what you say.
If living beyond the age we were designed for is the cause, I wonder why the American Cancer Society says:
By 2030 the incidence rates among people ages 20 – 34 years will increase by 90% for colon cancer and by 124.2% for rectal cancer.
If living beyond the age we were designed for is the cause, I wonder why the American Cancer Society says:
By 2030 the incidence rates among people ages 20 – 34 years will increase by 90% for colon cancer and by 124.2% for rectal cancer.
My dad had liver cancer which was detected early. We went with liver transplant and 3 months later, cancer reoccurred in lymph nodes in his lungs.
Now, he's on immunosuppressants (tacrolimus and everolimus) for organ rejection.
Can immunotherapy still be tried on him?
I've been working with a team* on an open-source analysis pipeline tool to assist researchers and oncologists in identifying specific neoantigens used in cancer immunotherapy. Given a patient's sequenced tumor/normal genome, it uses a set of prediction algorithms and the public Immune Epitope Database to produce candidate neoantigens for synthesizing the vaccines used in clinical interventions or research.
We just released a browser-based client to assist users not comfortable with constructing the long and complex command-line arguments used with most bioinformatics analysis pipelines. It also provides a REST API that makes it easier to integrate into existing research/clinical pipelines.
If you're working in this area of research/treatment please check it out to see if pVACtools can be of use to you!
http://pvactools.org
EDIT: Just received a writeup in GenomeWeb:
https://www.genomeweb.com/informatics/wustl-software-offers-...
* as a user-interface designer/developer
We just released a browser-based client to assist users not comfortable with constructing the long and complex command-line arguments used with most bioinformatics analysis pipelines. It also provides a REST API that makes it easier to integrate into existing research/clinical pipelines.
If you're working in this area of research/treatment please check it out to see if pVACtools can be of use to you!
http://pvactools.org
EDIT: Just received a writeup in GenomeWeb:
https://www.genomeweb.com/informatics/wustl-software-offers-...
* as a user-interface designer/developer
This is cool. Who is the main target user for this? Biotech companies? Academic researchers?
Both. It's currently being used mainly by academic researchers, and biotech companies are evaluating it as well.
How does it perform compared to any in house software at biotech companies? Or are the main users companies that specialize in making cell therapies / peptide vaccines and you just help them figure out which vaccines to make?
Am just interested bc i have a few friends involved in neoantigen / shared tumor antigen cell therapy companies, and did some consulting work for a company that had tech for delivering nucleic acid therapies and was considering getting into oncology, but didnt have in-house sequencing or antigen identification expertise. Mostly intellectual interest at this point
Am just interested bc i have a few friends involved in neoantigen / shared tumor antigen cell therapy companies, and did some consulting work for a company that had tech for delivering nucleic acid therapies and was considering getting into oncology, but didnt have in-house sequencing or antigen identification expertise. Mostly intellectual interest at this point
The biggest difference between academic tools and those in industry is that they're sinking major funds into producing (expensive, hard to produce at scale) training data. That, in theory, should allow them to develop better algorithms for actually predicting which mutations in the tumor are going to be the best (immunogenic) targets. This tool, and several others like it, are modular enough to allow you to plug in whatever prediction algorithm you like, while still getting the benefit of all the other steps.
The cure for cancer already exists. We've had it for ages. It's THC found in the cannabis plants. See research from, among others, Compultense University in Spain.[1]
Many people suffering from various forms of cancer have been cured by using cannabis oil made from cannabis with high THC concentrations.
[1] https://youtu.be/1miGzTwK28U
[1] https://youtu.be/1miGzTwK28U
killing things is bad mkay.
prevent instead of cure. solve the root cause.
" “The tidal wave of data is still teaching us fundamental concepts about the interaction of the human immune system and human cancer.” "
So, if they still learning fundamentals. -> impact of actions based on inaccurate or incomplete knowledge, is unknown.
in programming this kind of practice would lead to bugs / undefined behaviour etc. - imagine what kind of shit that would mean for human health...
It'd be nice if they had cancer prevention studies instead of cancer cure studies. kthx
" “The tidal wave of data is still teaching us fundamental concepts about the interaction of the human immune system and human cancer.” "
So, if they still learning fundamentals. -> impact of actions based on inaccurate or incomplete knowledge, is unknown.
in programming this kind of practice would lead to bugs / undefined behaviour etc. - imagine what kind of shit that would mean for human health...
It'd be nice if they had cancer prevention studies instead of cancer cure studies. kthx
Many of the DNA mutations which cause cancer are essentially random and impossible to prevent. The human body is not a simple deterministic computer system.
If this were true, all I could express would be gratitude biologists don't think like programmers.
Often the alternative to trying a treatment that you don't fully understand is death.
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While we're still trying to sort out the root causes, a lot of people are dying. So we're trying to stop them from dying, even while trying to find root causes. (Society as a whole can work on more than one thing at once.)
When dealing with a software bug you have to reproduce the issue before you can definitively "fix" it.
Not true. (It is often possible to understand the cause by just looking at the damn code.)
Humans, and every other life form have an undocumented, undesigned self executing specification that consists entirely of the most reticulated, self referential spaghetti code compatible with successful reproduction and it’s not just riddled with Heisenbugs, they’re core parts of the machinery of how everything works. We’ll get there eventually but it’s going to take an exceedingly long time.
You are looking at human readable and annotated code, not what is compiled for the computer to run. Imagine finding bugs by looking at binary. DNA is more complex than 1 or 0, it could be ATCG. There are 3.2 billion nucleotides in the human genome, and we are still a long way from understanding the nuances of the DNA 'programming language.'
Maybe for superficial bugs in small toy programs. But a real bug in any sophisticated program requires a bit more than looking at the code most of the time. User feedback, log/trace data, performance data, system events data, memory dumps, etc.
Of course the bug could be in proprietary software your code is using. How would you fix that by purely looking at your own code?
Of course the bug could be in proprietary software your code is using. How would you fix that by purely looking at your own code?
(The article blithely says "remissions measured not in extra weeks or months of life, but in lifetimes". It's a little over-reaching since we just don't have that much long term data yet; these therapies haven't been around for "lifetimes". As a result we often prefer the term "durable remission" to "cure".)
I also want to emphasize how few patients have this outcome. It sucks. It sucks to have ads on bus stops and TVs that say, "Ask your doctor about Keytruda", but when they ask me, I know it has such a tiny chance of turning them into that laughing family playing in the grass. We test for and hope for the genetic markers that indicate certain immunotherapies are more likely to work spectacularly, but the vast majority of patients don't have those markers. Similarly, most patients with leukemias or lymphomas do not respond to CAR-Ts.
We still try these immunotherapies, though, because there's often evidence of some modest better outcomes, and also sometimes you get lucky. I think I mentioned this on HN in some other context, but one of the breakthrough discoveries around pembrolizumab was because of a "Hail Mary" in late stage colorectal cancer; all the patients progressed & died in the study except for one, and she held the key to the genetic derangement that made that subset of cancer particularly sensitive to checkpoint blockade -- leading to FDA approval for pembro for all cancers with that derangement. As this article mentions, there is now a massive number of trials studying these therapies in various subsets of patients, or in various combinations and permutations with traditional therapy, because short of "cure" there's still improved survival which can often be very meaningful.
It's exciting. It's inspiring. It's frustrating & heartbreaking.