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Immune discovery 'may treat all cancer' (bbc.co.uk)
625 points by sjcsjc 30 days ago | hide | past | web | favorite | 154 comments

Original article - https://www.nature.com/articles/s41590-019-0578-8

Very interesting finding indeed, these T cells seem to (not fully confirmed) target cells with abnormal mrtabolism, which is one of the hallmarks of cancer in general (most cancers at least).

This solves one of the biggest problems with immunotherapy, which is that if a cancer is not different from regular tissue in any fundamental way that the immune system cannot recognize, then it can't fight it. This is why melanoma is the poster child of immunotherapies (skin cells get mutated a ton due to UV so skin cancer has a lot of mutations to differentiate it by). If this cell stands further scrutiny, it could potentially be a very general therapy option indeed.

Potential caveat is that cancers typically find a way to generate resistance, and markers of abnormal metabolism (at least as detected by this MR1 receptor) night be easy to suppress, in which case this might just become one in a line of multiple treatments. That might still be good enough though.

> cancers typically find a way to generate resistance

Resistance is a neat thing.

I remember (and I'm sure someone will reply with a link to it, since I can't find it) reading a story about a fellow with a very seriously antibiotic resistant bacteria infecting his chest. It resisted everything they had. Researchers found a phage that would attack that specific bacteria- but alas, the bacteria became resistant to the phage as well!

Fortunately, the bacteria had limited dimensions in which to change. The changes needed to become resistant to the phage made it no longer resistant to at least one of the antibiotics. It could not have its cake and eat it to. With both attacks against the bacteria ongoing, it was defeated.

What I'm implying with all this is that yes, the cancer may become resistant to this therapy in question but in doing so it may be forced to become less dangerous, or less resistant to other forms of attack. It does not change merely from "not resistant" to "resistant" but from "form A, which is not resistant" to "form B, which is resistant", and "form B" may have a lot of other consequences.

Stuff like this gets used in cancer treatments, too, with combination therapies [1].

Even more interesting are drug holidays: cancer becomes resistant to drug A by evolving a new clone that uses some other metabolic pathway unaffected by the drug but is less efficient. Stop drug A, the first more efficient clone takes over again. Give drug A again and there is no resistance for a while.

[1] https://www.oncode.nl/news/one-two-punchmethod-published-in-...

I always wondered, resistance is an energetic cost as it tends to disappear without constant selection pressure. Why not infect someone with the non-resistant strain, let it outcompete the resistant strain inside the body and then kill it with antibiotics?

In general the patient is only being treated because the infectious agent is doing some kind of damage (makes them sad/sick/dead...) So the fear is that before the non-resistant strain has supplanted the resistant one the patient has become too (sad/sick/dead)

Can you link to this phage paper please. I'm about to start a project looking at phages.

https://www.vox.com/future-perfect/2019/5/14/18618618/phage-... is not the one in remembering, but it mentions the same effect.

> deploying phages can cause the bacteria to evolve in response, and that evolution sometimes involves switching from being antibiotic-resistant to being sensitive to antibiotics.

There's a few big stories like this. Chances are, in the next 25 years you may find yourself being treated with phages.

It’s my understanding that cancer stems from malfunctioning of our own cell processes, rather than from something that is viral/bacterial.

For that reason it seems wrong to think about cancer as “developing” resistances - I don’t believe that cancer is something that evolves/mutates.

Turns out I’m wrong! Cancer does undergo natir selection and develops resistance:


and they can be viral in nature, see oncogenic viruses e.g. HPV (cervical cancer)

It's true that cancer is made of human cells but it can still evolve on it's on. Evolution applies to anything that can reproduce while making small changes between generations. Cancer cells do this better than healthy ones, at least within the time scale of a single human life. In some species cancers have even evolved to become contagious and a single tumor has spread to thousands of hosts. https://en.wikipedia.org/wiki/Canine_transmissible_venereal_...

I'm kind of curious why those priors led you to this conclusion, as I can't follow it at all. I understand that you have already figured out that it is wrong, but I'd like to understand what made you arrive at the wrong conclusion in the first place.

Evolving is how it became a cancer in the first place.

> which is one of the hallmarks of cancer in general (most cancers at least)

It may well be the definition factor, at least some people think so: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/

If I remember their argument correctly, cells that "only" reproduce anarchically present little danger (benign tumor) if they don't also do so at an abnormally fast rate / metabolism.

Most cells stay in the same place, die when told to and don't make more copies. Necessarily some of your cells don't obey one or more of these rules (you wouldn't last long if your blood cells weren't endlessly copied for example or if they stayed in one place). But if all three rules get broken you've got cancer.

The cancer I had when I was young, Hodgkin Lymphoma, is one extra rule broken because the lymphatic cells already don't stay in one place and makes extra copies of themselves - which is why it relatively often occurs in young people. One copying error and the "Die when told to" feature breaks in the new copies and now you've got cancer.

Sorry but this is just false. Everyone has "cancer" all the time because these "mistakes" happen all the time. The reason why someone gets the medical condition, "cancer", is because for some reason, the immune system stops cleaning up these rouge cells. That could be a huge infection or injury, general decay of your body, etc, causing a cancer clump to form. Once cancer reaches a certain size, it will develop mechanism, like acidity, that will inhibit immune response regardless of whether the immune system would now classify the cancer as a threat. In any event, cancer is a very complicated condition, with many different causes. It's unlikely there will be a one-size-fits-all solution.

Well the position being discussed, different from the current consensus, is that what sets apart the "cancer" condition from routine mutated cell line is metabolism, not immunity to the immune (!) system.

In that spirit, subsequent mutations that confer resistance can be seen as a consequence of this abnormally high metabolism rate that overwhelm the system and also cause increasing mutation rates.

In conclusion, while cancer may indeed become a complicated condition to treat, the root cause thus defined is rather simple. Whether this paradigm is valid and useful is an open question, but the article being discussed sure seems to point that way.

This is true for most stationary cancers before they turn malignant.

Immune cells are already resistant to each other, and especially to stress. Additionally, they have pieces of genetic code that are manipulated during their life and potential to become self-reactive with no activation. If they lose anergy and apoptosis, it can be enough, and there are many paths to activate them into mitosis.

Immune cells can become a cancer just by their number and statistics of error. Just big leukemia is but a symptom but has potential for first stage cancer.

"If I remember their argument correctly, cells that "only" reproduce anarchically present little danger (benign tumor) if they don't also do so at an abnormally fast rate / metabolism."

Forgive this (very tortured) analogy, but I think there is a lesson here for would-be extropians who think society will simply tolerate a few vampires here and there.

Specifically: they'd better be living lives of quiet, impoverished contemplation ...

> Potential caveat is that cancers typically find a way to generate resistance

It's randomness. Theoretically speaking every possible combination could happen. So you should be able to have a Cancer cure, a cancer resistant to that, another cure, another cancer, etc.. at least until you cover all of the possibilities.

The goal is to have science become faster than physical mutations. You generate medicines faster than you generate resistant mutations.

It's randomness with causality; each momentary mutation may be random, but that mutation must be possible based on the prior state. So while it may be possible (even probable) for a perfectly resistant cancer to exist, it's much less likely for a causal chain to exist that allows for that.

I thought we learned our lesson about "paradigm-changing" scientific results released to the media simultaneous with initial publication a while back. The paper was published today, and only available behind a pay wall. Yes, this is exciting, but what they appear to have is a better way of tagging cancer cells so the immune system will attack them. This is one round of rodent studies in immunosuppressed mice, for which the abstract only claims "enhanced survival". There is no reflection or information from anyone who isn't actively on the team. This is a press release before a funding cycle, not science. "May treat all cancers?" Please.


How many times in the last 10 years have we gone bananas on HN for an immunotherapy wonder drug just to find it’s another casualty of the current unable-to-reproduce crisis in current science?

Remember when CD47 monoclonal antibodies from the Stanford trials were going to save millions of lives? What a time to be not yet dead that was.

The poster above is correct. Wanting this to be something wonderful doesn’t make it so, and anyone familiar with the subject matter knows this deserves skepticism. This is getting upvoted because it sounds good, not because there’s solid evidence it has legs.

I’d love for this to become a high efficacy treatment for millions of people, but we’ve had the same thing play out so many times now that it’s impossible to be excited.

This is what usually happens:

They’ll try it in the lab, and it’ll kill cancer.

They’ll inject it in mice, and it’ll kill cancer.

They’ll try it on people, and it’ll reduce the size of their tumors for six-to-eight weeks before they start growing again.

I’ll remember to check back in a year to to see if this is even still a thing.

* temporarily

Reducing the size of a tumor for six to eight weeks (especially via a new method) could actually be an important result. Many cancer drugs only result in temporary remission when used in isolation, before the cancer out-evolves the drug and comes back. However, using multiple drugs simultaneously (combination chemotherapy) and using the drugs after surgery to kill remnant cells can have a far larger impact. Many of the drugs that can now 'cure' certain cancers in combination only provide brief remission by themselves. (Disclaimer: my only knowledge of this comes from the book The Emperor of All Maladies)

Fair point with regards to combined therapies.

The Emperor of All Maladies is one of my favourite non-fiction books. As long as you can get through the human experimentation. That’s hard going (and horrifying).

Kindle edition appears to be £1.49 on Amazon.co.uk https://www.amazon.co.uk/Emperor-All-Maladies-Siddhartha-Muk...

I think that your post is a little bit too cynical. It is not like CD47 has disappeared, and many clinical trials are ongoing currently (15 trials currently recruiting), some with quite positive result (36% of complete response in heavily pretreated patients phase I study) (https://www.nejm.org/doi/full/10.1056/NEJMoa1807315). Other immunotherapies have saved many people something that you cannot dismiss. On the other ends translation from research to an available treatment is a very long path, but we should be excited every time a treatment save a person that should have otherwise died.

Some more details at https://www.telegraph.co.uk/science/2020/01/20/immune-cell-k...

> The team says human trials on terminally ill patients could begin as early as November if the new treatment passes further laboratory safety testing.

This is what I like to hear! People die daily from cancer, treatments like this with promise should be an option even if it's a long shot, the people are about to die anyway, it can only do good, for them or for science.

I definitely agree making it available is a good thing.

However, I'd take exception to 'it can only do good'. I've had a loved one opt for experimental treatment that was ineffective, and made the last months of his life more painful and separated from his family (treatment was in another city). I'm not saying we would choose differently if we were faced with it again, but in some respects I wonder if it was more a service to our peace of mind at having done all we could than it was for his comfort or happiness.

Mind here that it can also be for the patient's peace of mind. My grandfather was faced with a similar dilemna, terminally ill from pancreatic cancer, with a long-shot to try to cure it. The doctors were wonderfully frank about the potential for failure and "time lost"; even still, he opted to go down fighting. Alas, his liver wasn't strong enough to sustain the treatment, and it just ended up killing him faster.

He was a spiritual man and didn't seem regret the decision, but his family had a harder time with it. They were arguing for something closer to hospice, and wanted to take him traveling to enjoy the last months of his life in relative peace. In the end, that didn't get to happen.

There will always be a twinge of regret, I think. One can always look back and ask, "what if we had done it this way?" But it was the way he wanted to go, and I think the knowledge that he had tried everything that he could helped him to find peace.

I'm glad that your grandfather was happy with his decision. But from a policy perspective, there's a question to be asked about whether it makes sense to spend tens or hundreds of thousands of dollars on treatments that likely kill people faster. Even if that is what those people want, their needs have to be balanced with others who need the scarce resources that are allocated to the health system.

(On the other hand if this was an experiment and it just didn't go his way, that's another story. We need brave people to accept these experimental treatments sometimes to find whether they work.)

If that treatment didn't exist, your loved one would have opted for some other experimental treatment, no? So the existence of said treatment didn't make their life worse relative to that particular treatment not existing. (Rather, the existence of a class of experimental treatments for a particular cancer that maybe don't work, makes life worse for people, but once there's one, there's no harm in adding more, only potential benefit in at least one of them maybe working.)

I'm happy for all the progress being made with cancer. I wish we would also make progress on diseases that attack the nervous system for which we seemed to have made next to none. Alzheimer's, ALS, MS, Parkinson's, Hunnington's Disease, Kennedy Disease, Muscular Dystrophy, small fiber neuropathy, even benign issues such as essential tremors have no cure, and some of these are painful death sentences.

We seem to know so little about how our bodies work. There are no bio markers for some of these or early detection and little idea what are the causes or the important details of what's happening as the disease progresses.

I can imagine that if some highly efficient cancer technique pops up, a vast amount of money would be freed to fund other fields.

As a matter of public health, we should really be focusing the vast majority of our efforts on cancer and cardiovascular disease. Odds are that most people will end up dying of one or the other.

I recently spent time in hospital, and came away convinced that the one thing that could reduce the greatest amount of human suffering would be a really good 24/7 painkiller without long-term side effects.

Time after time I saw patients pleading with a nurse for more pain relief, and the answer came back, "You can only have so many in a 24 hour period, so you have to wait for another hour before I can give you any more."

The number of people I saw on one small ward who had hours each day full of really bad pain convinced me that pain relief would be one of the best places a philanthropist could spend money. If you're in that much pain you can't think properly, can't enjoy life, and it's all ultimately unnecessary, because, once a doctor and a patient agree there's something wrong and what to do about it, additional long-term suffering doesn't add anything to the experience.

People can have cancer. They can have arthritis. They can have a bad back, or kidney stones, or pancreatitis. I do think all those should be cured if possible. But the one constant misery for so many people, even if someone simply has old age - is pain.

I've been a full time patient for 32 years. We've come full circle on pain management. Again.

Wait a bit, the next cycle of oversteer will start soon enough.

Not excusing it. Just explaining.

I encourage everyone to figure out what works for them proactively. Because eventually everyone will need it.

Mental health [1] should be on that list. The amount of suffering as well as economic losses from mental health issues are overwhelming.

[1] Ideally we should work towards broader / more fundamental goals such as "well-being" and "meaning", but that is even more difficult.

I agree mental health should be allocated higher priority than it is. I can't find a great source, but this listicle[0] claims the top categories of conditions in terms of disability adjusted life years (DALYs) lost are:

  1. Arthritis.
  2. Heart disease.
  3. Stroke.
  4. Cancer.
  5. Mental health conditions.
  6. Diabetes.
  7. Nervous system disorders.
  8. Pregnancy.
  9. Accident.
  10. Developmental disorders.
Whereas the top causes of death in the US[1] are:

  1. Heart disease.
  2. Cancer.
  3. Accident.
  4. Chronic lower respiratory disease.
  5. Stroke.
  6. Alzheimer's.
  7. Diabetes.
  8. Influenza and pneumonia.
  9. Kidney disease.
  10. Suicide.
Given that heart disease, stroke, and cancer top both lists, IMO, it makes sense from a pragmatic POV to focus on those two.

Side note: I was surprised to see arthritis at #1 on the DALYs list. Seems like more research is needed here, as well.


[0]: https://www.cheatsheet.com/health-fitness/this-awful-disease...

[1]: https://www.medicalnewstoday.com/articles/282929.php

I think one thing that's overlooked in Cancer research is how much ground has been, and will continue to be broken in terms of basic biological research to solve the problems required.

To even define and understand the problem properly we have to solve a bunch of things. Then to get to a solution a bunch of other things need to be figured out and can be integrated into humanities knowledge base. On top of that things can be dragged in from other fields to get a sense of how biology responds at various scales: genetic, tissue, organ, system, whole person. It's a perplexing and fascinating disease to grapple with.

It's worth mentioning that just because something tops a list of conditions, doesn't mean money/effort is best spent there. The true measure is expected benefit per $ spent. Some conditions prove particularly resistant to research efforts, while others might be comparatively cheap to cure or alleviate. In those cases you are better off focusing on the 'easy wins' and moving to the more difficult problems once the biggest and fastest gains have been made with the comparatively easier conditions.

Psychology research is certainly important, but not in the same way as cancer research.

For mental health, what's primarily needed is more access to therapy.

First, mental health issues account for a huge amount of suffering and societal expense.

Also, this is a commonly misunderstood issue. We are increasingly finding that "psychological" issues have strong links to physiological issues. Here is one example (of many):


Autoimmune disorders can lead to a huge variety of neurological/psychological issues. All work on better understanding of the immune system is going to help many overlapping disorders.

What have previously been seen as "psychological" issues are, for these disorders, only marginally improved by therapy. Therapy can help someone cope, but root causes might be based on immune system issues.

I could of course be wrong, but my own unfounded suspicion is that in a few years we will find that a lot of current mental health therapy was rather stone age. Much may be replaced by more fundamental treatments to eliminate the source of basal ganglia (or other structures) inflammation that led to the psychological disorder.

This view, that mental illness is about psychology is kind of like what people refer to as the "god of the gaps" defenses of theism. Far too little is understood about mental illness, but no matter how much we learn about metabolic, autoimmune, or other disorders that affect mental function, there will always be some cases that aren't understood and people will still say that there are psychological explanations. By definition, essentially, mental illness is everything that can't otherwise be classified as a physical or neurological disorder. But all that it is, is a drag on actual efforts to solve problems.

As far as comparing to cancer, it seems plausible to me that some measurement like "quality adjusted years lost" (or impaired) could show it's more significant than cancer. I hesitate to say we need more research for anything, because unlimited funding leads to garbage research. But good research is needed. One of the most interesting developments in the last couple decades, I think, was "optogenetics" - techniques that allow scientists to manipulate neurons in a living subject by using light. But just funding more research may just mean torturing a few more mice to no purpose.


We need better, safer, anti-psychotic medication.

We need better, more effective, treatment for entrenched eating disorder.

We need better treatments for treatment-resistant depression or anxiety disorders.


Currently most mental health medicine is like throwing darts in the dark. We clearly don't actually understand why some medications work for some people but not others. If you go through the medicine path then I can only wish you the best of luck - finding the right medicine is life changing but it's a long arduous struggle to find it currently.

Not to mention the side effects...

> We clearly don't actually understand why some medications work for some people but not others.

There are plenty of psychoactive drugs where we have no understanding of why they work at all. Lithium is one of the oldest, most successful, and best known medications for bipolar disorder, major depression, and schizophrenia, and we have no idea which of the many effects it has on the body actually contribute to stabilizing mood.

Psychedelics and mdma seem to be very promising in this area.

In terms of reducing DALYs, I agree. Depression and anxiety disorders are the most common mental health conditions[0], and most respond quite well to psychotherapy.

But, we also need better access to addiction treatment (decriminalization would be a huge step here), more drug research, and a huge push to remove the stigma of mental health conditions in general.


[0]: https://www.nimh.nih.gov/health/statistics/global/global-dal...

I disagree that simply access to therapy solves the problem. I don't think we have a good understanding of the many causes and factors that affect the wide variety of mental health issues people face.

I think the rates of depression and anxiety are indicative of a problem, and the answer isn't just to throw resources at it.

citation on that? my understanding is that therapy is our best option but that's it's unreliable and about as good as our drugs.

Look up the side effects of common medications for severe mental illness and ask yourself why anyone would take them if therapy was a more effective alternative. If you have no idea, let's just say they can kill you in various terrible ways, or damage your body and brain irreversibly, including causing tumors, and/or put you in a living hell, not to mention cause diabetes, and yet, popular medications have been around for 25 years or longer. It's not because there is a conspiracy of doctors or drug companies, and it's not because there are good alternatives, and it's not because positive thinking fixes everything.

Well said. It's frustrating to be on a train of drugs that become less effective over time, necessitating the roulette wheel of trying new ones again. And when they work, you don't feel better, you just feel less worse. Furthermore, they work by deadening the edges of your personality, so while you don't feel worse, you're unable to feel as happy as you are when you're not on them. They're the worst, but they're why I'm still here commenting, so I take the good with the bad.

ah yeah, I wasn't talking about severe cases. For severe cases medication is better than therapy.

Severe cases are the only ones where treatment matters. Anything works for problems that aren't severe. Preferring therapy to acupuncture is just a personal preference.

The way you identify a serious case is where the forming and/or maintenance of normal relationships is seriously impaired. Therapy is a way of providing needed human contact. It's just not addressing the underlying problem.

> Anything works for problems that aren't severe

That's measurably not true.

The consequences of not working (so long as it's not counterproductive) on an non-severe (so long as not also progressive) case may be less than a severe case, but that doesn't mean that everything works in those cases.

Usually the phrase is "severe and persistent". Things that aren't severe and persistent are tolerable and get better and worse, so whatever you do or experience, it can appear to help.

There's a difference between “help” and “appear to help”, and measuring to distinguish the two is a central function of clinical science.

> Therapy is a way of providing needed human contact. It's just not addressing the underlying problem.

citation needed.

Which part of that needs a citation?

All of it?

There are two sentences that appear to be separable. So I don't know what you mean by "all of it". You think therapy does not provide human contact?

well therapy can be administered online or in a self-directed manner and still be shown to work.

Edit: Further you implied that the purpose of therapy is to provide human contact not just that it involves human contact.

I hold out a lot of hope that the resurgence in psychedelic research may lead us out of a large part of our mental health crisis.

Yes. Mental disorders account for many years lost to disability. https://www.nimh.nih.gov/health/statistics/disability/us-lea...

Sort of, but not smoking, diet, and exercise get you pretty far on cardiovascular disease.

And cancer for that matter.

But from a brutally pragmatic point of view, the point holds.

Does diet and exercise really get you that far against cancer though? My sense is that it helps but only a fraction of the amount that it does against cardiovascular disease, is that right?

I asked this as well, literally Googling up "Does exercise prevent cancer", and what I found isn't all that great:


>Nearly all of the evidence linking physical activity to cancer risk comes from observational studies, in which individuals report on their physical activity and are followed for years for diagnoses of cancer. Data from observational studies can give researchers clues about the relationship between physical activity and cancer risk, but such studies cannot definitively establish that being physically inactive causes cancer (or that being physically active protects against cancer). That is because people who are not physically active may differ from active people in ways other than their level of physical activity. These other differences, rather than the differences in physical activity, could explain their different cancer risk. For example, if someone does not feel well, they may not exercise much, and sometimes people do not feel well because they have undiagnosed cancer.

I would really like to see some proper studies done. Unfortunately, seeing friends and otherwise healthy, physically active people passing away from cancer at a relatively young age does not inspire hope at the moment.

Not that I'm disagreeing with the limitations of observational studies, but it's not quite that simple. Cancer Research UK describes being overweight or obese as the second biggest preventable cause of cancer (after smoking):


In particular, there appears to be a causal link between being fat and an increased risk of some cancers via several identified mechanisms, though of course this whole area is a subject of ongoing research.

Given the well-understood links between a healthy diet, getting enough exercise, and maintaining a healthy body composition, it's important to pay attention to both diet and exercise in order to minimise cancer risk, even taking into account the other effects.

> Overweight and obesity are associated with at least 13 different types of cancer.


Is "exercise" just a euphemism for not being overweight then? You can be skinny and not exercise, or be overweight and regularly exercise.

Obligatory reminder that correlation is not causation.

Of course, avoiding obesity is advisable for everyone where possible, for all kinds of reasons.

But there are cases where a complex physiological problems (particularly autoimmune issues) can contribute to obesity and cancer risk.

Such cases are quite possibly more frequent than is generally understood, given how many people try and fail to lose weight through diet and exercise.

I doubt any disease will grant you more energy than what you've eaten nor conditions that substantially improve the bodies efficiency. It's important to remember that exercise alone won't burn off that many calories. It's diet that is primarily responsible for that

It’s an argument that is as old as the hills and relies on the assumption that the body functions like a simple furnace, which of course is false.

Metabolic rates vary significantly, and rates of absorption of nutrients and consumption of energy vary a lot as a result of factors such as inflammation and endocrine function.

Calories in/calories out may still ultimately be true when you boil it down far enough, but the factors influencing and intervening in those processes are vastly complex and strongly affected by diseases and dysfunctions that are very common.

Thyroid disorder (which can include cancer or a precursor condition) is probably the most common/known, but just one of many.

The short answer is yes, they can make a meaningful difference to risk, but as ever with cancer, the long answer is that there are a lot of risk factors and they aren't the same from one type of cancer to another. I'm not a medical expert, just someone who's supported cancer research for a long time and has a lay person's understanding of the issues, so I'll leave it to more knowledgeable people to comment any further.

I don't really like the idea of abandoning people suffering from "rare" diseases. ALS sucks so much. It is a horrible thing to be told you have ALS, you'd wish you were diagnosed with cancer or cardiovascular disease instead.

There's huge interest in fighting Alzheimers and other neurodegeratives among the pharmas. Alas, there's been nearly zero success on that front after more than 20 years of effort. Until more cutting edge research can suggest more promising approaches, it's unlikely that Big Co R&D spending will climb. For now, it's going to be up up to governments to fund the big risk takers — academic labs and their offspring startups.

Until more cutting edge research can suggest more promising approaches, it's unlikely that Big Co R&D spending will climb.

Alzheimer's is a bad example.

There is in fact evidence of success with treatments that treat underlying brain infection rather than preventing amyloid beta plaques from forming. 20 years of barking up the wrong tree may be at an end soon.

More specifically, Herpes Simplex. I don't remember where I read it, but I recall a paper arguing for Herpes being one of the viruses considered for causing (some cases of) Alzheimer's. It's even considered that amyloid beta may be a natural response of the body to the infection, not the cause: https://www.alzheimers.net/alzheimers-and-herpes/

As far as I know there's no letup in searching for treatments for neurodegenerative diseases. Spending remains high because the payoff will be huge.

This makes it sound like it's all been in vain. Negative results are just as much if not more progress than the end of resolving the cure

At least for Alzheimer's there has been some hopeful advances recently[0]. Given the state of the low research funding allocated for it (especially compared to the disease's prevalence), that's pretty good progress I would say (and hopefully enough to spur more investment into solving it).

[0]: https://www.alzforum.org/news/research-news/2019-year-hope-a...

You'll be happy to hear that, in recent years, the funding for Alzheimer's disease has boomed. My lab does a lot of research in AD and it is probably the fastest growing area of funding by NIH, from 600 million in 2015 to 2 billion this year[0]. Also, note Aging is another real growth area and a lot of Aging programs have AD/Dementia as a sub-focus. [0]: https://report.nih.gov/categorical_spending.aspx.

[Edit] from 1B to 4B if you count subcategories. Expect good things in the future.

IIRC we've at least made some progress towards slowing the progression of symptoms for some of them. Would be awesome to see some huge breakthroughs though.

The progress of these are independent from each other.

Unless society is willing to allocate a larger percentage of GDP towards medical research it really is zero-sum which diseases get funding and which do not.

Yea, but if Cambridge and Somerville Massachusetts allowed more housing construction, it would be easier for medial research labs to get staff.

Not totally. Those conditions have money and people working on them that could be put to work on cancer and heart disease.

> Hunnington's Disease

Assuming you mean Huntington’s, there’s a whole bunch of very promising treatments being trialed.

Yes I had a typo, I can't edit the post now. I'm glad promising treatments are on the way.

this describes a t cell receptor that recognized and killed cells from several cancers while sparing healthy cells

theoretically this could may made into a therapy by taking t cells from patients, modifying their DNA to express this receptor, and then readministering the modified t cells to patients

there are two FDA approved drugs that use this basic approach. however, this only works currently in "liquid tumors", not "solid tumors" like breast cancer, lung cancer, prostate, etc

This article gives a nice, simple explanation as to why solid tumors are more difficult (scroll down to the chart): https://www.the-scientist.com/features/the-next-frontier-of-...

if this works, then the first challenge listed in the chart would be mitigated. however the challenges of a suppressive tumor environment and sufficient delivery to tumor cells is still a major unsolved challenge

The title says may, but it's a very optimistic title anyway. From the article:

> However, the research has been tested only in animals and on cells in the laboratory, and more safety checks would be needed before human trials could start.

> Lucia Mori and Gennaro De Libero, from University of Basel in Switzerland, said the research had "great potential" but was at too early a stage to say it would work in all cancers.

The abstract closes:

> These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.

So it hasn't come (to the journalists) from nowhere.

Relevant xkcd: https://xkcd.com/1217/

A vlogger I follow on Youtube (Mark Carriker) was diagnosed just over a year ago. He's recorded everything. From first diagnosis, surgery, radiation, chemo, immunotherapy, trial drugs and now Hospice. It's heart breaking to see someone go through this. Hopefully, a cure will be found soon.


This sounds very promising and also sounds like this case just a couple of days ago where a young boy was removed of cancer cells. I'm not sure if it's the same kind of treatment.


One key quote:

> "At the moment, this is very basic research and not close to actual medicines for patients."

That seems to contradict what the paper's authors have to say on the matter:

> Prof Sewell said the ‘right people’ are now interested in developing the potential new therapy and said progress could now move ‘quite fast’. The team says human trials on terminally ill patients could begin as early as November if the new treatment passes further laboratory safety testing.

Source: https://www.telegraph.co.uk/science/2020/01/20/immune-cell-k...

Some level of skepticism is certainly warranted, but it's not impossible that this is way closer to "actual medicines for patients" than you might think.

At the same time, this could make chemo and radiation therapies obsolete long term.

Leaches and amputations without anesthetic were once “state of the art”, and it feels like that’s where we’re currently at with cancer therapies. CRISPR is knocking on the door of amazing potential.

I'm wondering if there's a "Can I use"-kind of summary for proposed cancer treatments available somewhere; presenting the various methods attempted, which kind they target, do they work in vitro, in animal models, are they currently in clinical trial, effectiveness results, link to papers, etc.

Can we just get an npm package already?

Ugh... have you stopped following the Javascript ecosystem for the last three hours? We use YARN or NPX now. /s

> The findings, published in Nature Immunology, have not been tested in patients, but the researchers say they have "enormous potential".

then later:

> However, the research has been tested only in animals and on cells in the laboratory, and more safety checks would be needed before human trials could start.

The abstract for the original article notes:

> ... An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. ...


What does that second sentence mean?

Also: TCR == T cell receptor

Here are some the descriptions of the related methods currently researched:


“ Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes.[1]” (from Wikipedia)

“autologous - adjective - (of cells or tissues) obtained from the same individual.”

Perhaps this discovery could end up going the other way, with those newly discovered T-cells being the culprit in auto-immune diseases. Boosting their action would be too dangerous to use as treatment for cancer, but knowing that they are there may lead to new treatments for auto-immune diseases.

And where does this fit into transplant rejection? Perhaps MR-1 differs enough between people to cause problems. This reads like the early days of a discovery that could lead anywhere.

As someone with Crohn's and who knows people with all sorts of similar (maybe?) autoimmune diseases, any nugget of hope for something besides immunosuppressant treatment (meaning our bodies are always welcoming of other infections/sickness) is welcome.

Fortunately, the paper shows that this particular treatment doesn't attack normal cells, but it may cause trouble longer term (which is one reason additional safety studies are required before human trials).

Also, I'm pretty sure there is already an increase in autoimmune disorders after current immuno-oncology (IO) treatment. Patients should certainly have that information before treatment.

Anyone know how we HN readers can help this effort?

Is there some open source scientific community/repository like GitHub? (Where people can pull down the latest data and ideas, and add to them, then push our changes back to the main scientists.)

> Where people can pull down the latest data and ideas, and add to them, then push our changes back to the main scientists.

A repository of ideas from non-experts will probably slow down things rather than help them. I'm not dismissing the idea outright; perhaps there's a way structured inputs from patients and caregivers can be helpful (again with some review mechanism so that real researchers don't have to wade through irrelevant data.)

Thanks for the feedback. So maybe the main scientists would host the repository, with their ideas and data. Then we could review and perhaps add to the main scientist's ideas, or find problems with the data. Or add more data with our own experiments. In other words, a collaborative approach. Maybe the main scientists could limit contributions to people who met a certain threshold of earlier verified contributions. Or let other people corroborate and verify before the main scientists even saw the layperson's contributions. Just an idea, open to improvements!

How do you feel about opening up your company's git repositories to non-experts? I think an adequate example of the difference in expertise between an average software developer and a cancer researcher means we should probably open up your git repos to a 9 year old.

Most of the people in this thread have about as much reason to "share ideas" with cancer researchers as a 9 year old has to share ideas about your line-of-business form-over-data web application.

The fact is that research at this level results in such specialized knowledge that not a lot of people would be able to contribute. Additionally, the pressure of academia would probably prevent scientists from disclosing publishable results.

It’s not quite a ‘one size fits all’ if you have to take cells and genetically modify them for every patient. Sounds like it would be very expensive. Amazing nevertheless if it really works.

There’s a similar treatment already, CAR-T. The “one size fits all” aspect here is that this receptor mechanism may possibly work with many common solid tumor types (*in mice), whereas CAR-T’s efficacy is limited with solid tumors, but can be dramatic with leukemias and lymphomas. There’s a related therapy for prostate cancer, Provenge (https://en.m.wikipedia.org/wiki/Sipuleucel-T), but it’s merely a life-extending treatment and not the cure that CAR-T can be.

Couldn't one develop BiTEs (Bi-specific T-cell engagers) for this receptor? That would be cheaper and off the shelf for every patient.

My girlfriend (who is in medical school) actually brought this up to me when I was talking to her about how it seemed that not only the rate of R&D was increasing, but the time to market was also falling dramatically. It's cool to see these kinds of developments being utilized so much faster

The upgraded cells would be grown in vast quantities in the laboratory and then put back into the patient.

What I would like to see is a world in which doctors and researchers ask "Why isn't your body already making enough of these and what can we do to help it crank them out in sufficient quantities?"

My understanding is that cancer kills you late enough in your life to has little impact on your ability to reproduce, and thus fitness in the evolutionary sense.


These are deaths / 100'000 people. It's a bit difficult to judge precisely in that resolution, but death by cancer is <1%/year before the age of 40. That was roughly the life expectancy (assuming you made it past childhood, big if), for humans during most of their evolution.

So the likely answer is that it never mattered to our body (or survival) to combat cancer effectively.

> death by cancer is <1%/year before the age of 40. That was roughly the life expectancy (assuming you made it past childhood, big if), for humans during most of their evolution.

My understanding is that Paleolithic peoples generally had a life expectancy of about 50-60, assuming that you survived childhood. The development of Neolithic probably lowered life expectancy somewhat (since, basically, people eating an agricultural diet are essentially chronically malnourished until sometime in the Early Modern).

Nowhere have I seen any indication that the life expectancy of humans, at any point in time, was as low as 40.

I'm not by any means an expert, but the very first Google hit (wikipedia as usual) gives:

> Based on Neolithic and Bronze Age data, the total life expectancy at 15 would not exceed 34 years.


Which in turn cites this article: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajpa.1330300...

There's a lot of bad stats out there that are based on averages, which are distorted by the high infant and childhood mortality rate of pre-industrial humans.

Or, alternately, we produce plenty of them normally in our youth so as to keep cancer from getting a good hold and we develop deficiencies that reduce their production as we age and this allows cancer to go from whatever stuff causes it floating around the body randomly to full-blown tumors and the like.

Either way, your framing has zero bearing on my point. If they can produce them in quantity in vats for purposes of combatting cancer, why not produce them in quantity in the body? That's my point.

> Either way, your framing has zero bearing on my point. If they can produce them in quantity in vats for purposes of combatting cancer, why not produce them in quantity in the body? That's my point.

I tried to answer "why are these not naturally produced in quantity by your body".

Are you asking why the scientists didn't alter human bodies to artificially produce these cells in quantity inside the body? No idea, but that does sound a lot more difficult/dangerous than producing them in a vat?

That wasn't what I asked:

"Why isn't your body already making enough of these..

And I don't think it is dangerous to wonder what the hold up is and try to do research to answer that question. But it seems like no one here is actually getting what I'm trying to say.

It's late. I'm tired. Whatevs.

Human evolutionary fitness goes beyond individual reproductive fitness, for kin-selection sort of reasons. That's why e.g. women are generally capable of living well beyond menopause

Yes, but if you're dead by 50 anyway for unrelated reasons, there's still not selective pressure to combat cancers that only kill you at 60+. That's regardless of your individual reproduction or your contribution to the group's fitness.

This is a much harder question. Also much more risky -- now you need to affect multiple interconnected systems and pile on side effects. I'm sure there are an infinite class of possible treatments that if produced in your body, would render it incompatible with being alive (or human).

Imagine you need to make Excel export csv documents with dots instead of commas, and there is no easy option to toggle. The app was grown, not designed, so same commas are used in all kinds of other places in the output and in memory and even in the byte code and even in processor cache buffers. Only sane option is to add some post-processing.

Well, sure, if you need to dump a million cells into the body to combat a ginormous tumor, that's complicated and hard on the body.

That's not really what I'm thinking about though.

Oh no, millions foreign cells is actually much easier on the body than tweaking a million little ratios that affect everything or outright rebuilding parts to manufacture those in-house.

I don't think I'm at all managing to convey what I mean here.

I wonder if this could have anti-aging uses to identify and remove cells dealing with metabolic dysregulation.

One anti-aging speedup would be that long term safety of HGH therapy would be much less important if cancer would be easy to cure.

Peter Thiel started HGH therapy in 2014 because ,,cancer would be cured in 10 years anyways''.

It seems to me like his prediction is coming true (maybe we'll need 5 extra years though).

Why does more testing need to take place? I would be willing to bet the majority of people currently dying of cancer within the next month or so would have zero problems testing it for them. So much bureaucracy. People need help now.

Vast majority of new cancer treatments do not end up improving survival times and generally come with significant, unpleasant side effects. Of the small minority that are found to be a net benefit, most are just barely worth it: very modest extension of life expectancy with sufficient toxicity that many well-informed patients will nevertheless decline them.

This is not just chemo either; immunotherapies can be brutal.

Like most new cancer therapies, this will surely get “expedited” status from the US FDA, which will enable as fast a development as imaginable, like FIM (first in man) within the year. If it delivers on its promise, it will receive initial approval for those with advanced metastases of the initially targeted forms of cancer within a year after that.

A major question is the cost of the therapy. If it equals CAR-T, which it closely resembles, it will NOT see rapid adoption until the price per treatment falls below CAR-T's current bill of $500,000 US.

Beating 500k/patient seems like an approachable target. When my mom had lung cancer, when it recurred it came so fast there was never any time to think about speculative treatments. Of course you'd pay anything to save your loved one.

I went from 0-60 on prostate cancer in a few days last year when my dad was diagnosed at stage 4 (he’s much better now). I was surprised to find that getting into clinical trials is not so difficult and they’re well catalogued; as an example, check out https://www.cancer.gov/about-cancer/treatment/clinical-trial.... Generally, it seems that promising therapies advance pretty quickly, and oncologists seem to stay current. So, I don’t think there’s quite the level of bureaucracy as you may suspect.

That said, with trials there’s a good chance a patient will wind up in the control group (sad trombone), and a lot of new treatments don’t work all that well, or merely extend survival for a few months in exchange for several side effects. A LOT of trials are also simply studying the efficacy of the combination of known treatments; these trials are safer bets, but they’re also unlikely to provide one with a miracle.

With immunotherapies, keep in mind that side effects during treatment can be severe and potentially fatal. Basically, if you have late stage cancer and treatment works, you almost die from the toxic effects of your immune system kicking into overdrive and blowing up all the tumor cells in a few days. There’s a ton of supportive therapy. If a new immunotherapy like the one in TFA showed promise, all the necessary supportive therapy acts as a limiter on rapid scale-up, even with perfect knowledge sharing and patient access.

What is the theory here with MR1? They say it’s a metabolic indicator, but it’s a MHC. Looks to be involved with B3/NAD. Does a cancer cell just run out of NAD so MR1 doesn’t get presented?

Side note: I’ve been self-experimenting with high doses of niacinamide, and experiencing some weird side effects, possibly immune-related, like angular chelitis. Probably unrelated.

Might be inhibiting sirtuin activity... http://www.jbc.org/content/277/47/45099.short

Please tell us more.

High dose of NMN are supposed to be helping develop some cancers.

angular chelitis is totally new to me. Are you on retinoids by any chance?

I took a lot of cod liver oil once it started, maybe a little bit before too, so I suppose it could be that. I did a lot of research into what would increase NAD levels, and it’s all pretty inconclusive, so I figured niacinamide was as good as any other B3 in the pathway. I later found that it chelates with some minerals, so I may be giving myself a deficiency.

Yes a deficiency is far more likely than an autoimmune disorder

Neil Peart, David Bowie, Gordon Downie. I’ll know we’ve made significant advances if a celebrity can use his/her status to get cured.

How’s a former President?


(Although there’s no indication his status led to his cure, of course. With immunotherapy, the requisite status seems to be “can become patient of a decent clinic,” not “former leader of the free world” and/or legendary rock god.)

So who has the mutation in their T cells already?

If I need this right now no matter the outcome, what do I need to do?

Did they find a cure for Dunning-Kruger syndrome yet?

Er, wasn't that the plot of I Am Legend, "... three years later ..."

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