I took care to read the fine submitted article (based on a press release) and most of the preceding twenty-some comments before replying here. Comments to the effect that we often see stories like this based on press releases that don't translate into clinically useful treatments are correct. Anyone who has been on Hacker News as long as I have has seen dozens upon dozens of stories about breakthrough medical treatments that don't turn out to be breakthroughs.
As usual, here in this thread I recommend Peter Norvig's article "Warning Signs in Experimental Design and Interpretation" about how to read research reports in general.
Medical research is slow and painstaking. There has been genuine progress in medical research in my lifetime. (My mother was a nurse in our state's largest research hospital, and medical research was a subject of dinner table conversation in my home.) But false starts have been numerous. There are a great many medical treatments that have been proposed in my lifetime that have not been proven to be both safe and effective for treating what they purport to treat. Peter Norvig's article provides a good checklist of all the ways that optimistic initial reports can turn out to be wrong, of which "too few subjects" especially applies here.
I reply over and over and over again on threads like this here on Hacker News because I did grow up with a strong interest in medical research--and some anecdotes about medical research that went awry--and because I know that legitimate medical researchers sometimes find their work hyped by the university press office or funding agencies far beyond their own more cautious statements. But here on Hacker News we may as well learn how to be discerning readers. Let's not just believe what we want to believe, which is the cognitive bias all human beings have, but let's test factual statements for strong evidence and make sure that the experimental procedures reported in some new study mentioned in a press release really support a grand conclusion. It's too early here to say "Drug made from toxic weed kills cancer" in a way that is safe and effective for a broad range of human patients for even the one kind of cancer that is mentioned in the article submitted here. I'm glad someone is working on this, but it's way too early to declare that we've found a cancer cure through this work.
Upvoted! What I really miss (in general, not just here) is a certain level-headedness when it comes to things like this. I know it is hard to avoid the hype since it is everywhere and omnipresent. but as technical people I still want to believe that we can avoid it and think things through before we open the champagne. We can do it in our own domains, why not in others too?
This study details the use of a peptide-drug conjugate; these are drugs with peptides (small proteins) chemically conjugated to cytotoxic drugs.
The idea behind these conjugated drugs is that the peptide portion of the drug hones in on a specific biological target and the conjugated cytotoxic drug then kills the cells that have been recognized by the peptide (think warhead and payload). In this case, the peptide recognized prostate-specific membrane antigen, which is expressed on prostate cancer cells, and the cytotoxic drug was one derived from Thapsia garganica, the toxic weed (cytotoxic drugs being isolated from plants is nothing new, of course).
A more common class of these conjugated therapies are called antibody-drug conjugates[1], where an antibody molecule (instead of a peptide) is linked to a cytotoxic drug. There is currently one of these drugs, Brentuximab vedotin, FDA-approved for the treatment of cancer[2]. There are many more under preclinical or clinical development.
So if prostate cancer has metastasized, and we target the cancer, do we do so at the hazard of exposing the healthy prostate cells to the same fate?
Do the cells of other cancer-prone organs produce similarly specific antigens?
If so, how do we avoid the situation where we eliminate (for instance) melanoma tumors of the brain and lungs only to have the patient's skin kill itself off completely?
I think that all of your questions come down to two core concepts: therapeutic index and antigen stability.
For therapeutic index, you want to identify and target antigens that show the largest difference between cancerous tissues and normal tissues (i.e., antigens with a large therapeutic index). In other words, you'd want your drug to bind to an antigen that's present at a higher level on the prostate cancer cells than the normal prostate cells, such that the normal cells are spared.
For antigen stability, you ideally want your drug to target an antigen whose expression is maintained in metastatic lesions. In other words, if a cancer metastasizes from a primary site to a distant organ, and the antigen your drug targets is maintained on the cancerous cells that have made their way to the distant site, then that is a more therapeutically amenable target then one whose expression is lost upon tumor metastasis.
Do those explanations answer your questions well? Let me know if you'd like me to clarify more.
I really hate it when people express a predictable sentiment along the lines of "herp derp, digg/reddit/HN cured cancer again! It must be Tuesday!" While it's necessary to be reserved, scientific progress, especially in biomedical fields should be celebrated, not derided.
We need more researchers in the world working on these problems that benefit us all. Thinly veiled mockery of their work and the progress they're making is really unsavory and possibly quite discouraging to someone who's thinking of going into this field.
Just be grateful that progress is being made; one day you may directly benefit from that experimental drug mentioned in the article.
The complaint is levied against the reporters, not the scientists. If we actually heard from the scientists, we would generally get reserved statements about progress and good indicators. That turns into a weekly cure for cancer that doesn't really exist once we hit the "scientific" press.
In this case, it looks like the complaint is poorly founded. This is a real breakthrough working on people cancer (as opposed to mouse cancer).
When the headline "Drug made from toxic weed kills cancer" really means "Drug made from toxic weed kills [for some definitions of kill] cancer [for some definition of cancer (in mice)]", the scorn on the reporting is richly deserved. These sort of linkbaity headlines only serve to undermine the solid work and real achievements of the scientists doing the research.
The thing is - we really only need one cure for a particular strand of cancer. Once we've actually done it we've done it. Bearing this in mind I think these stories deserve a fair amount of optimism.
What do you mean by "strand of cancer"? In any given tumor, there are multiple cells lines each with their own set of mutations. That's what makes curing cancer so difficult.
This is a review of a very interesting paper recently published. 50 women with breast cancer had their tumors sequenced. The result? 1700 distinct mutations and the most common three mutations only showed up in 10% of patients.
My personal belief is that cancer will never be "cured" in the literal sense of the word. Many cancers will become chronic conditions like AIDS where life expectancy is reduced, but people diagnosed will still get to enjoy a majority of the average life span.
If there are so many strains of cancer for each patient, those patients do have multiple diseases and we should treat them with multiple drugs.
There's a medical device that lets you test the response of the patient's biopsy to multiple drug combinations.
I wonder if scaling this by:creating huge libraries of cancer drugs that only passed animal safety trials, using this test device to find the most effective combination of large amounts of drugs(maybe even combine drugs that fit the genetic profile of the biopsy strains) and using the combination but carefully managing dosage not to create toxicity , could be useful and practical to fight those mutation rich cancers ?
refurb is right - we essentially do this now,
our limitations are:
- Cost of sequencing
- Toxicity of current drugs in combination
- lack of suitable drugs
- lack of patient trials
More on the last:
This is on which everything depends. Medical ethics 'bends' a lot of allowances with regard to anti-cancer drugs because of the stakes but you can't just start introducing things willy-nilly. A new drug does not a cure make. And drugs have interactions, sometimes serious. Using one new drug may lead to some shift of the survival curve (or at least shrinkage of tumour, maybe it is now more susceptible to Surgery/Radiation or is just going to give them better quality of life) but adding additional drugs may reverse this trend if they are not properly researched
All this requires money
All this takes years
But a surprising amount is already in progress. Sitting in on case conferences with practicing Oncologists and Radiologists, they have combinations of drugs with strange names 'R-CHOP' etc - have a wiki - to roll out against standards, are always reciting the latest literature, trying to get patients into new trials that show promise, all in the hope of continually shifting the survival curve further to the right
That's actually not a bad idea, because we kinda of do that right now, just very inefficiently.
I'm sure 10-20 years from now, we'll have a collection of drugs that target specific mutations in cancer (the number is already getting large).
Doing it via a med device is actually not a terrible idea. You can at least screen for the mutations, but predicting how the drugs will act in the human body (especially in combination) is much tougher.
However, with many forms of cancer, there are very few options, so higher risk method of treatment are much more tolerable.
yes it's called chemo sensitivity test, but how many people ask for it? also you can test for expression of various genes, which would help eliminate drug that are know not to work with a particular gene being expressive.
unfortunately, today patients know too little; there is too much reliance on doctors, but I am working to change that.
When it comes to medical science, I would take skepticism over optimism any day. Many promising drugs have made it through the first rounds of trials, only to fall flat later on. Let's save the optimism for drugs that actually make it through to market.
That's like reading the announcement of new software and saying, get back to us when they discover all the bugs.
Naturally, there will be adverse events due to toxicity. But unless you have some particular insight into why this should be much worse in this case than for other drugs, merely mentioning that there will be toxicities doesn't really advance the discussion. At least, not as written.
You would be surprised how much you might come to regret that choice. Especially when you realize you've only slowed the cancer's growth rate and allowed it to metastasize throughout your body. If you are lucky you will die before you lose major cognitive functions. If you aren't you will slowly lose a grip on everything as you become dependant on others just to survive.
There are things much worse than death, especially for the ones you leave behind.
I wish publications would wait for Phase 2 data before publishing sensationalist headlines like this. In this case, they have yet to even complete enrollment for the Phase 1 trial.
Most Phase I work is exploratory and things like statistical rigor and blinding participants are ignored (and for good reason, those things don't come cheap). Phase I data is useful for toxicity data, but I wouldn't trust Phase I efficacy data in the least.
You're exactly right. In grad school, a friend of mine working on a PhD. in biological sciences once casually told me he'd discovered 4 new antibiotics in the course of his research. Of course, I was floored, until I thought to ask what his definition of "antibiotic" was. Turns out that at the stage he was working on, all it meant was the compound killed bacteria, not that it was at all useful for treating infections.
be cautiously optimistic. It's real research that has worked in animal models. It remains to be seen whether it will be as effective in humans.
Additionally, shrinking a tumour is a long way from a cure.
For example - The drug Ipilimumab (melanoma) was shown in clinical trials to increase median survival from 6.4 months to 10 months. Some people may have disease-free recurrence for significantly longer than they would have, some may actually be 'cured' (Disease-free survival for 5 years is a fairly standard medical definition of 'cure'), others die at the same time, or a week, or a month, later than they would have anyway.
For all of these drugs, there is no magic bullet, the tumour will evolve around the mechanism.. My understanding of the subject (final year medical student) has lead me to believe that an immunological approach will be best (See my post which links to a nejm article further down the page)
hey robbie, i am working on a crowd sourced site to find evidence based treatment options for a disease. i would like to get feedback from you as you are a med student. would you reach out? my contact is my uesrname at gmail
Shrinking tumors is good. It's also important to stop cancer from metastasizing. I guess this drug might end up being used as a long term "maintenance" therapy.
But I personally hope for a cancer therapy which goes beyond playing whack-a-mole against tumors. Maybe one day they'll gain a more fundamental understanding.
Maybe one day they'll actually know why the body begins to form these tumors, why its built-in anti-cancer mechanisms fail or become overwhelmed, and, most important, how to restore or unblock the body's own ability to control and limit cancer cells.
I don't think there is any great mystery there - mutation and copy errors create the initial conditions that lead to loss of function of tumor supressor genes or in of function in oncogenes, caused by known risk factors and some unknown risk factors we are still elucidating.
There isn't a much more fundamental understanding that can be gained. We know all of this, we are beginning to elucidate the chromosomal translocations and karyotypes that seem to appear in certain families of cancers (and a specific cancer type will have the same 'assortment' of chromosomal typings)
all that remains is to continue to design increasingly effective anti-cancer agents, one part of which this article is explaining.
I don't believe there will be a single magic bullet, however treatments that have an immunological basis (See this NEJM paper that offers incredible hope for CLL - http://dx.doi.org/10.1056/NEJMoa1103849 )
Or antibody based Rx coupled to cytotoxics or radiologicals as an adjuvant Rx, as well as the success of the designed molecules such as Imatinib etc all bode well for the future.
Unfortunately the big C will evolve it's way out of many of these therapies (Imatinib etc inhibit fusion proteins created in aberrant cells that lead to proliferation, slowing but not necessarily stopping growth, so the cell evolves around it)
But is there any hope that medicine will find a way to enhance or strengthen any of the body's mechanisms for controlling these mutated cells and this erroneously copied DNA?
yes - sort of - that's what the paper is about essentially - it details a gene therapy approach where T cells are removed, taught how to recognise surface antigens for leukaemia cells and re-injected into the body, leading in 3 weeks to a complete clearance of his CLL which he had had for 13 years and which was close to killing him.
Now THAT is a cure. So the immune system may be the key to doing this.
but for what you are asking:
Things we can do now:
- We can take things that lessen the chance of this damage occurring in the first place (Anti-oxidants, good diet, 'everything in moderation', etc)
- We can modify our lifestyle to avoid risk factors (Cut smoking, drinking, drugs, bad food)
- We can actively do things that are likely to strengthen our immune system and the constant immuno-surveillance that it performs, that already stop us from developing cancer at age 1 (Exercise, good sleep)
Things we Can't do:
: Because of lack of precedent, failure of mechanism, or lack of scientific enabling principle (Your 'dead end')
- We will probably NEVER (although that's a strong word in scientific progress - let's say not for the foreseeable future, 25-30-40 years) be able to take a pill that will REVERES the damage once it's done
- We will probably NEVER (with the usual caveats) be able to take a 'simple' drug molecule, as we understand the word to mean at the moment, to kill cancer cells wherever they are in the body
: Because we just don't understand enough about how to do this:
- We lack enough understanding to say what would happen if we were potentially able to design a molecule that acted as a 'backup' to the main TSP, p53, and were able to somehow deliver it into the cell to be a 'backup' tumour suppressor and make the cell autodestruct if it got out of control
I could go on and on about theorised Rx'es, things we do now, things we are just bringing online, and how I think it will all go down but that's probably enough for a buried response in HN that few people will ever read.
However if you have any more specific questions or I can help you understand something else, ask away
Not necessarily. There was some sad findings that tumor shrinking chemicals caused fragmentation and mobility.
I've recently talked with a student researching on Warburg Effect http://en.wikipedia.org/wiki/Warburg_effect , linking switch in metabolic regime (mitochondrial damage) to disabling the apoptosis mechanism. Their idea is to repair mitochondria so that cells will terminate themselves as usual using nanoparticules.
A while ago someone on HN suggested that whenever he reads about something like this he creates an alert in google news for keywords, and then forgets about it.
It sounds like it wouldn't be perfect (some good brain cells would die), but it'd likely be a heck of a lot more selective than existing methods of dealing with brain tumors. And certainly better than an alternative of letting the tumor grow any more.
It sounds like this could work on cancerous tissue in its infancy, which is probably the most promising thing. Imagine a potential vaccine for cancer, just enough dosage to kill that first bad group of cells.
Brain cancers mostly disrupt the blood brain barrier, Which is an organised tissue structure that exists to preserve the microenvironment of the brain against normal fluctuations and insults.
Cancer is disorganised tissue that doesn't know how to produce nice neat blood brain barrier tissue organisation
Correct. This tumor-mediated disorganization of the blood-brain barrier (BBB) is what enables cytotoxic drugs to reach larger cancerous brain lesions, which explains why these growths often show a clinical response. Under normal circumstances, many cytotoxic drugs cannot cross the BBB.
if you are looking for treatment options for brain cancer, please see http://pubmedly.com/demo there's the standard temodar and then there's the other options that may have better outcomes, like novocure
Nice to know, but I bet It won't be used widely soon, no matter if it works or not. Medicine wants keep cancer pacients alive, not cure them. Curing is not profitable. If they (and people themselves) wanted us not to be sick, almost nobody would be.
"Medicine" is not a singular entity sitting in a dark lair cackling to itself, its a wide variety of people and institutions that all have their own ideals and motives. Most are in it for the money, but to a somewhat lesser degree than in other industries.
What thinking of "Medicine" as a singular entity blinds you to is that while not curing people might result in more money for medicine as a whole, a cure for cancer would certainly make a whole lot of money or whatever entity came up with it. They'd have to choose the good of their industry over their own good and the good of their patients to a degree I would find incredible to do otherwise.
Yeah, I know that there are many institutions and people. But those people create a whole system. And I guess there are not so much players in that market that can develop such cure without any help. Research itself is expencive and nobody can just state he created cure for cancer and let people test it. They need much money to make it legal medicine. Can you tell me how much people/institution has enough resources to do that?
Moreover I guess medicine is quite homogenous as a science. What if way they are looking for that cure is simply wrong? What if law specifies wrong ways of testing drugs? Is it easy to change the law? If way of looking is wrong, I guess it's extremely hard to get money for research since people who decide rather trust the science. If law don't let find cure, I think it's even more difficult.
Because see how healthy man can be if only he want? Ever tried? Moreover technology evolved so much and healthcare seams to work worse than before. Think about it, science can tell what happens billions of killometers away and what happens in subatomic scale and it can't find out how human body works enough to cure most common diseases? It doesn't convince me.
And why not to believe? There are many people doing bad things. There are wars, animals are treated like garbage. Why not to believe someone want to make bussiness on disieses?
How about remissions, why nobody believe they occur for a reason? People are too stupid to find out that reason? I don't think so. Or maybe am I wrong and scientists try to find out why they happen?
Why basis of caring about health in mainstream medicine now are meds and vaccination and not healthy diet and doing sports? I use no drugs and I don't get sick. I used to, before i started to care what I eat and what I do for my health. Noone ever told me to do what I've done. I rather seen commercials of drugs that are not healthy and not realy work.
Does anyone care about that psychedelic drugs relieve cluster headaches (where no other good working med is known)? Anyone cares MDMA decreases symptoms of Parcinson disease? Is it so difficult to find out why? I mean, if anybody except single scientists care? I don't mention how great can they impact on state of mind.
Hemp is great painkiller, medicine for insomnia, and others. Why I can't use it to relieve my pain or to help myself fall asleep? Why medicine use much more dangerous drugs if hemp could be used? As far as I know It's illegal because someone don't want to admit it's useful for medical reasons.
Medicine is so broken. For me someone want it to be broken or people in medicine are stupid. I can hardly believe they are so stupid so I'd rather believe second option. The fact that some people always wanted to enslave somehow other people. We had explicit enslavement and religion. Why medicine wouldn't be next one?
You assume people are doing this for "bad reasons". Or to make money.
It's not so. Medicine just doesn't know any better.
Each year they get better and better, but overall they barely know anything.
The body is VERY complicated, and people just don't understand it very well.
You think someone "cured" cancer but did not sell it to make extra money. Not so - there are so many people with cancer that they would make a HUGE amount of money by curing them all. And there are new cases all the time.
Remember that even the most profitable drug it's only for 20 years, then is not protected anymore.
Yeah, but if no drug is not realy needed, you can't earn on it. Groceries and gyms does. Sorry, change of lifestyle made very big impact on my health. My immune system works so well cold can't become enough serious even to make me feel bad. I practicaly don't get sick. Moreover I noticed mood lift, better work of brain, no insomnia anymore, I have much more energy.
My body seems to know what is good for it - it prefers healthy food and don't accept stuff are not healthy. It even doesn't want beer anymore. ;) Why the hell nobody told me about that? If science made reserch on that, no flu vaccination or pro-immune drugs would be needed! Even more - there would be less cancers, heart diseases and so on. Nobody deny diet has big impact on those disieses, but noone what to use it. THEY KNOW how to do better, THEY DON'T!
And I'm not the only one. I know guy who treated asthma and alergy, which is in fact possible, in some cases, but no doctor even tried to do that.
And since he found information how to do that and I did - surely there are far more people does better than mainstream medicine. Think about it, some regular guys with no medical knowledge does better then proffesional doctors. Doesn't that mean there's something wrong with healthcare? Is there realy no reason to be sceptical about how it works?
The profits for a drug to cure every kind of cancer would be astronomical. You seem to have the assumption that when cancer is killed it cannot return. But, it can. Mutations happen often and because of this, cancer would happen often. Cancer kills people. You do not want your customers to die. It would be more profitable to release a cure and have people take it whenever cancer is found because it is certain to return.
You mentioned that changing your lifestyle has made you healthier, but that has been mentioned to me by my doctor every time I visit! Eat healthy, get plenty of rest, and exercise. We have heard this many times before. This is not some magical secret to a healthy life. Many people simply do not possess the willpower to do it. There are companies that profit from unhealthy choices because our bodies crave those unhealthy choices, but it does not mean there is some conspiracy by scientists to prevent drugs from reaching the market that can cure cancer.
The cure would be more profitable because over a long enough time line, cancer returns. People that get cancer are often predisposed to getting it in the first place.
Well, I won't argue any longer if cure for cancer would be more profitable or not. I'd need some professional analysis. I'm not proffesional so I don't know. Anyway they already take much money for treatments that doesn't realy work. It's quite good bussines. For sure it's very easy and safe strategy to keep status quo. What if cause of cancer would be found and it would no longer come back after treatment? Working cure wouldn't be so profitable then.
Yes. I wrote that everybody know that people should live healthier. But there is big problem. Telling is not enough. How people who never had proper lifestyle and diet can know what "healthy" realy mean? They only can assume that if they feel like they felt before they are healthy. Maybe not perfectly, but they are. This assumption is simply wrong.
Do you know people who live healthy? It seems to be highly addictive and spread quite fast. The only condition is that people have to see that those one who live healthy are far more healthy than they ever asumed. For example one of my frieds i live with in one flat needed only few weeks of watching how do I eat to decide to improve his diet. He's happy he did that. He loves oatmeal for breakfest too (also my habit). I doubt if someone who live healthy would like to stop. If you go to doctor you don't see what to expect so you don't change anyhting.
As usual, here in this thread I recommend Peter Norvig's article "Warning Signs in Experimental Design and Interpretation" about how to read research reports in general.
http://norvig.com/experiment-design.html
Medical research is slow and painstaking. There has been genuine progress in medical research in my lifetime. (My mother was a nurse in our state's largest research hospital, and medical research was a subject of dinner table conversation in my home.) But false starts have been numerous. There are a great many medical treatments that have been proposed in my lifetime that have not been proven to be both safe and effective for treating what they purport to treat. Peter Norvig's article provides a good checklist of all the ways that optimistic initial reports can turn out to be wrong, of which "too few subjects" especially applies here.
I reply over and over and over again on threads like this here on Hacker News because I did grow up with a strong interest in medical research--and some anecdotes about medical research that went awry--and because I know that legitimate medical researchers sometimes find their work hyped by the university press office or funding agencies far beyond their own more cautious statements. But here on Hacker News we may as well learn how to be discerning readers. Let's not just believe what we want to believe, which is the cognitive bias all human beings have, but let's test factual statements for strong evidence and make sure that the experimental procedures reported in some new study mentioned in a press release really support a grand conclusion. It's too early here to say "Drug made from toxic weed kills cancer" in a way that is safe and effective for a broad range of human patients for even the one kind of cancer that is mentioned in the article submitted here. I'm glad someone is working on this, but it's way too early to declare that we've found a cancer cure through this work.