Why Preventing Cancer Is Not the Priority in Drug Development
nytimes.com
nytimes.com
First of all, the basic science is lacking. The vast majority of animal models in no way resemble the normal process by which humans develop cancer. The models are designed to grow aggressive cancers extremely fast so you can test drugs rapidly, publish your paper and get the next grant. Even more than that, what actually takes place in the years before a cancer becomes clinically relevant is quite speculative. So a long term commitment to funding prevention research is needed from governments and funding bodies, because pharma can't fund this kind of basic science.
The other problem is that to do a good prevention trial, you need to identify people at risk. We aren't really that good at doing this (eg we screen ALL women above the age of 50 for breast cancer, we screen EVERYONE above the age of 50 for bowel cancer). There is some debate about whether screening in this manner is actually as worth wile as it has been made out to be, because it leads to over diagnosis without a survival benefit. So you have to be careful not to design an intervention that only prevents cancer in those who weren't going to be affected by it anyway. This is why you can't use surrogate end points - at the end of the day, for prevention, mortality is what matters. Are we going to give hundreds of millions of women drug X and make them suffer niggling side effects for 20 years because it reduces the rate of diagnosis of breast cancer? Definitely not - overall mortality is what matters (and quality of life).
It's not even a given that you can actually identify people at risk - some researchers think cancer is just bad luck (ie it is not predictable at all, or the predicting factors are unknowable). Even if this is wrong however, cancer risk probably involves weak effects from hundreds or even thousands of factors. We are very far from working all of this out.
A drug is probably not what we want. Actually a drug is really not what we want. They are too expensive and too much effort to distribute and monitor. Drugs also always produce health inequalities within and between nations. A holistic approach to improving our health and well being would be preferable, at least incorporating nutrition, exercise and psychology. Unfortunately the nutritional, exercise and psychological sciences are not hitting home runs in that regard, which is not surprising because they miss out on the billions we spend fighting an incredibly wasteful war on cancer.
As you wrote, cancer risk probably involves effects from many factors. However, I'm not sure how redirecting "billions" to, e.g., "psychological 'sciences'" serves to reduce the incidence of cancers that are essentially environmental in origin. Healthy lifestyle only goes so far; I suspect the vast bulk of cancers are due to environmental factors or are intrinsic to the human aging process.
Sure. Those generalisations are super easy but don't help a pharma company to design research. Which are which? What factors are meaningful? How do I isolate them and test against them? Is there even a vague chance this research leads to a drug that I can sell for $$$?
(also is there any evidence that a protein and vegetable only diet reduces the risk of cancer in a meaningful fashion?)
Maybe, or maybe not. When you actually have cause to investigate this stuff deeply, as I have, it's surprising to discover how little is known about these kinds of things.
If you could take 100 people of similar age and health and had them all "run eight miles a day with full pack, eat only protein and vegetables, have the mental outlook of the Buddha", and 50 developed cancer and 50 didn't, little is known about why any given person would stay healthy and another would get sick.
As you wrote, cancer risk probably involves effects from many factors. However, I'm not sure how redirecting "billions" to, e.g., "psychological 'sciences'" serves to reduce the incidence of cancers that are essentially environmental in origin.
Having researched this topic in great depth, I'm now persuaded by the medical researchers like Bruce Lipton and Rudi Tanzi who assert, with solid scientific evidence, that psychology - particularly subconscious emotions - are a major factor in determining whether a person will develop or recover from serious illnesses like cancer, diabetes, Alzheimer's, MS, ALS, etc.
Of course these ideas don't get much acceptance or affirmation from the majority of mainstream medical researchers, because, hey, everyone already knows that psychology and physiological health are totally independent, right?
It turns out we don't actually need to be redirecting "billions" to, e.g., "psychological 'sciences'".
It would suffice to let go of some of the unexamined assumptions and prejudices that prevail in the current research landscape, and pay some attention to the more open-minded researchers who are already investigating these things and coming up with promising findings.
... You've become convinced by this man.
> Surgical oncologist David Gorski has described Lipton as a crank who misunderstands evolutionary biology. He notes that some of Lipton's ideas start out based on research from epigenetics but he twists them into a "woo-sphere".
So could you cite some of the "solid scientific evidence" that you have referred to... because your appeal to authority seems to have failed you... :\
But a chronic auto-immune illness that became debilitating about 5 years ago, and a long, exasperating, and ultimately futile attempt to find treatment via conventional medicine forced me to consider anything in order to get well, and the method that got me well came via chiropractors and Lipton's ideas.
As of now I'm almost completely recovered, whilst others I know with similar conditions who have stuck with conventional medicine continue to be sick and frustrated.
So, scoff if you will, but had I not learned what I learned from Lipton, I'd have no health and possibly no life.
Now I understand the physiology behind my illness and my recovery, I believe those who say the same kind of approach could be effective for cancer - at least the ones that occur downstream of auto-immune illness (colorectal cancer for example). And I believe the anecdotes of people who've used these techniques to overcome cancer, because it aligns with my own experience. (Though let me be clear: I don't believe chiropractors can "cure cancer", and I don't have much time for chiropractic at all these days, now that I've found better and cheaper alternatives.)
But of course it needs more research so it stops being mere anecdotes and starts becoming hard data. That's the whole point of this thread.
As for "hard science" - all I can point you to are the books by Tanzi and Lipton, and Tanzi's research papers.
Tanzi is Professor of Neurology at Harvard University, and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital. He's been a leading researcher on Alheimer's for over 15 years, and much of his research and writing is focused on the role of emotions in genetic expression and the development of illness.
But he's co-authored books with Deepak Chopra and has been criticized by Jerry Coyne - so he can therefore be disregarded, right?
This is exactly my point.
I profoundly wish there were more hard studies (indeed I put quite a lot of thought into whether I could help facilitate some research based on my own experience).
I understand that Lipton's manner and Tanzi's link to Chopra make them easy to dismiss in the way that you have.
But the dismissals all seem to succumb to the "begging the question" fallacy - dismissing them because "we already know they are wrong" rather than engaging with their arguments and evidence.
I may only be a sample size of one, but significant numbers of people are recovering from illness by following the principles they espouse and significant numbers of qualified medical practitioners accept and endorse their ideas and research findings.
If more attention was paid to this research and if it were then to inspire further research, maybe the world would start making real progress towards overcoming the illnesses that account for most of the ballooning costs of the health systems in western countries.
Update: here's a link to a recent study linking emotion-focused therapies on telemere length in cancer patients. Telemere length is believed to be relevant in cancer risk and recovery potential: http://onlinelibrary.wiley.com/doi/10.1002/cncr.29063/full
You don't want people to dismiss it, but you give vague descriptions of what happened, what you did, and what the result was, and why you think they were related.
Seriously, if you wanted to be taken seriously, then engage the topic seriously.
I was simply backing up others' suggestions that psychology could play a significant role in serious illnesses like cancer, by pointing out that there are prominent figures with mainstream scientific backgrounds (Lipton was a stem cell researcher and medical lecturer at Wisconsin and Stanford; Tanzi is a senior professor of medicine at Harvard) who have written books explaining and documenting some of the science behind this idea and that I and many others find their work persuasive.
I wasn't seeking to win any argument with an appeal to authority (though you did, along with a straw man dismissal).
I was suggesting some sources of further insight that others may have chosen to pursue if interested.
Then in response to your combative reply, I explained that I have personal experience with the topic. Again, not trying to win any arguments with this, just indicating that I have cause to take this issue very seriously and research it very deeply (I've read far more broadly than just Lipton and Tanzi fwiw).
But still, in response to your demand for hard evidence I linked to one academic paper on the topic and I linked to more in another (far more polite) comment in the thread.
After that discussion I went searching for further journal papers on the topic and found this:
http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7...
Seriously, I have no dog in any fight other than that I was sick for a long time and now I'm making big strides towards to being very well. And I know there are many people - some I know personally - who are falling through the cracks of the medical system and it's very sad to witness.
I don't care much for any wars over the validity of "mainstream" vs "alternative" medicine. I consider most non-mainstream medicine ineffective and most alternative practitioners (including chiros) to be quacks.
But as a startup guy I'm comfortable with the idea that the most transformative ideas will often come from the fringes, and may well be sitting there already, just waiting to be explored. The fact that one of this year's Nobel Prize winners for medicine was for a discovery that came from traditional Chinese medicine should serve as an important reminder of that.
On the topic at hand: it's uncontroversial that psychology plays a role in the development and healing of physiological illness. The only questions are on the mechanics of how it works, the specifics of how it manifests in particular illnesses, and what techniques may exist or may be developed that could be effective in clinical settings.
In all sincerity, if you genuinely care about this topic and want to discuss it further, I'd be most willing to do so. I'd be happy to share more details about my own illness and recovery, and other sources of evidence that I've found useful.
You can find my details in my profile.
Like I said, I understand the skepticism as I was exactly that way inclined myself not so long ago.
But I'm also familiar with the kind of person who is more interested in picking and winning petty battles than learning about a topic through a good-spirited discussion.
So I'll finish by saying that while I accept my comments could have been more convincing with links to hard evidence (if convincing was what I'd set out to do), your rhetorical style is not of the kind that helps make HN a productive place to discuss interesting ideas, and thus seems contrary to the spirit of participation we try to cultivate here.
That said, I'm still happy to hear from you if you sincerely want to explore the topic further.
Your comments feature the following fallacies:
- appeal to authority
- poisoning the well
- begging the question
- straw man
- appeal to common belief
- appeal to ridicule
Needless to say, it's against the spirit of HN, which seeks to uphold the principle of charity as a means of working together to find the truth in the topic at hand.
Nevertheless, as requested I've provided links to evidence to support the point of view I was presenting.
I just wish it didn't have involve so much time defending myself against the hostility.
On the upside, I've learned more about the topic, I've developed further thoughts about how to help bring about further research, and I've been reminded just how much of a minefield the topic is and how cautious one needs to be around it. So, some good has come of it.
But seriously, if you value HN as a place of productive discussion, please bring a spirit of charity and enquiry.
Hopefully my followup comment adds some substance - though not links to one-off studies, as it's to broad a topic for that.
For you or anyone else interested, Lipton's The Biology of Belief explains the principles very well on a cellular biology level. Tanzi's books with Deepak Chopra (Super Brain and Super Genes) are probably more of an affront to credulity given the Chopra connection, but are there for anyone who can get over that.
Yes they are all pitched at the new age self-help market because that's the audience that's into this kind of stuff at the moment.
Hopefully that won't be the case forever, and signs are there that attitudes are starting to change.
It seems almost an accepted wisdom that mental outlook would play some part in recovery process. Think positive and you will recover/improve somewhat faster(this has been in popular press many times in last 20-30 years).
However, I have a hard time finding evidence that negative outlook makes you get a serious illness.
This is something that I see in magazines of dubious nature("The seven all-natural cures to dementia that your doctor is hiding from you!")
Are there publications with peer-review behind that?
http://www.wakehealth.edu/News-Releases/2013/Emotional_Stres...
http://www.ncbi.nlm.nih.gov/m/pubmed/18190880/
The process of stress leading to disease is fairly well-established and uncontroversial:
1) Any stress puts the body into fight or flight mode
2) When the body is in fight/flight, energy/nutrients are devoted to short-term survival, not long-term needs like immunity, cell-repair, digestion
3) After long enough in this state (chronic fight/flight) infections take over, cells break down, tumors form, etc.
If, for the sake of fond memories I allow my mind to wander, I feel my heart weaken in a second. There's a connection between some emotions and your organs. It's not far fetched that constant negativity could trigger this (I believe it's close to takotsubo syndrom, pain => bad hormones => change in heart tissue) and lead to very bad health overall.
I'm not at all saying we should give up on cancer research (I'm doing a PhD in the field at the moment). My point in the last paragraph is this: prevention is applied to healthy people, but taking pills to prevent a disease is quite an odd notion of 'being healthy'. We should think carefully if the pills4prevention paradigm is going to deliver us the sort of outcomes and lifestyle we really want. I worry that the whole idea encourages an almost absurdly narrow and reductionist view of human health.
Exactly. You can still get your cancer without BP.
"A holistic approach to improving our health and well being would be preferable, at least incorporating nutrition, exercise and psychology."
I'm all for being healthy, getting good sleep,and exercise, but I dont want to go back to blaming cancer on personality types, or a lack of certain vitamins.
Those holistic cancer commercials on t.v. are irritating. Once you have cancer, all that holistic, clean living doesn't matter--unless I've been reading the wrong studies.
I'm getting to the age where my rate of cancer goes up. If I get it, I'll get the stats of my survival rate; then decide if I want to treat it conventionally. Holistic treatments are out for myself.
I used to wonder why Steve Jobs didn't run to conventional medicine the day he was told he had pancreatic cancer. After looking at the survival rates, I kinda understand why he looked for someting else. Pancreatic cancer has a low cure rate. I belive Steve Jobs was trying to invoke the placebo effect with all that eastern/holistic medicine b.s.? I do believe in the Placebo effect. I think every doctor out there would tell their patient, whatever you do--try to belive in its success rate!" I do think conventional medicine is the way to go, but believe you will get better. Don't scour the Internet. Just do the treatments, and believe you will get better. Drown out the talking heads. They don't know why we get this disease in most people, and they don't know exactly why we get better.
I'm not being flipped about cancer. I'm just wondering how I will handle the diagnosis/treatment--if I get it, or anyone close to me does.
From a forbes article on the subject
"Jobs’ cancer had been discovered by chance during a CT scan in 2003 to look for kidney stones, during which doctors saw a “shadow” on his pancreas. Isaacson told CBS’ 60 Minutes last night that while the news was not good, the upside was that the form of pancreatic cancer from which Jobs suffered (a neuroendocrine islet tumor) was one of the 5% or so that are slow growing and most likely to be cured."
http://www.forbes.com/sites/alicegwalton/2011/10/24/steve-jo...
Even giving something like metafomin [1] where we have decades of knowledge is in practice impossible to give to healthy people. No new treatment stands a chance.
It is hundreds of different disease related to mutations in the function of cell division. Cells that don't need to divide, start dividing but the daughter cells are not the same as the parent.
In order to treat Cancer with a drug, you need to identify which of the hundreds of subtypes it is and give the right drug. Either that, or give people cocktails of lots of drugs and hope that you can identify the right one before the other ones kill the patient.
At this point there do not appear to be any magic bullets that will cure cancer, just lots of work and research to chip away at the problem, one subtype or one patient at a time.
And cancer appears to be inherent in what we are, animals. It seems unlikely that we will be able to change what we are sufficiently to avoid cancer. No vaccines are likely.
On the other hand, all the investment in Cancer research is paying off and is chipping away at this family of diseases. There are lots of reasons, not just new drugs, but some new drugs are part of the solution.
Maybe the human race is at a point where we have solved all the easy problems and now have a hard slog to chip away at the rest of them, bit by bit.
That’s one of the findings from the work of Heidi Williams, an M.I.T. economics professor and recent MacArthur Foundation “genius” grant winner, who studied the problem along with Eric Budish, a University of Chicago economics professor, and Ben Roin, assistant professor of technological innovation, entrepreneurship and strategic management at M.I.T."
I'm damn near 40, and the phrase "there's no money in a cure" has been around as long as I can remember. Heck, Chris Rock did a whole bit about it. [0]
Is this just putting good science behind that phrase? Is there anything new here?
[0] http://anonhq.com/chris-rock-on-big-pharma-no-money-in-the-c...
http://www.investopedia.com/ask/answers/08/broken-window-fal...
The usual reasoning behind "there's no money in a cure" is that you can squeeze a lot more money out by treating patients for years than by selling them a cure once. That's still a reasonable cynicism, but it's not what this paper was looking into.
Edit: another way of thinking about it is that if a company is maximally evil (economically rational), they would want to research early-stage cancer treatments because that would allow them to milk the patient much longer. Even with this incentive, they still don't do it, they research treatments that are faster to verify efficacy for.
At any point in time, patients have the choice across the spectrum of mitigations or cures. Cures are more difficult to produce but if they are available patients will choose them every time. Companies that produce mitigating medicine are counting on their ability to recoup investment before a cure materializes at some point in the future. If a cure becomes available, the value of their mitigation research goes to zero. Biomedical companies make bets that, if a disease looks particularly difficult to cure, mitigation will retain its value long enough to return a profit as a product.
Most biomedical research companies are looking for cures because it allows them to do an end run around their competitors and grab most of the profits. Every biomedical company wants a cure because it completely displaces competitive mitigation strategies and therefore allows them to collect virtually all of the profits. Mitigation is the fallback position when cures fail. But biomedical research is looking for the cure that will give the a naturally monopoly position by default.
I hope no one actually believes that, because it's really quite a stupid thing to say.
There are TONS of industries that rely on selling things just once to consumers, and yet they have a huge market. How often do you buy a new toilet for example? Yet there are tons of models with lots of competition.
There's plenty of money in a cure.
Hell, if you told cancer patients "we can control it, but it involves taking a pill once a day for the rest of your life. The cancer will not shrink, but it will never metastasize to other sites and you will not die from it as long as you take the pill." -- they will KILL to get ahold of it.
That would be the way for an evil company to extract maximum profit. And that's assuming there's a monopoly or a collusion between pharma companies (in reality, there is big competition).
Until that becomes a reality (if ever), people should shut up about cancer conspiracy theories.
Developing a drug is an economically difficult thing: Spend billions for the chance to win billions. The only alternatives to big pharma in developing these drugs are big government and big charity (Gates' Foundation et al).
Cancer affecting the old is not strongly de-selected for by evolution.
I also don't subscribe to the theory that individuals have to procreate to boost the survival of their genes. In reality it's a bit more complex than that, and even very old people can and do contribute to the survival of their children or their close relatives.
It's only a "priority for evolution" to prevent cancer before the better years for breeding have passed - and evolution has done a fairly good job with that. After breeding and a little time for rearing young in the higher life forms, evolution has no real use for us.
If Patent Monopolies Bias Cancer Research, Why Not Have Publicly Funded Trials?
http://cepr.net/blogs/beat-the-press/if-patent-monopolies-bi...
Or perhaps let's shelf this discussion at least until we figure out how to incentivize sustainable development of new antibiotics.
In fact, one extremely effective way to reduce cancer-related mortality would be to keep ignoring the problem with antibiotics. We may not exactly like the way that plays out though.
If it were just a question of funding it would be solvable.
Patents, copyright protections (yes, they're screwed up now, but better than without), infrastructure like roads or postal mail historically.
Just that US legislative process is spinning its wheels at the moment and for the foreseeable future.
Much of them require lifestyle modifications and regulation, unfortunately, which is admittedly very difficult to do. Still, I suspect investment in these areas would likely have a higher return on investment than R&D into broad preventative drugs.
(1) Smoking Cessation: Reducing tobacco use has a =huge= positive effect on cancer reduction - an order of magnitude higher than anything else we can do.
1 in ever 5 deaths of males over the age of 30 is due to to tobacco-induced illnesses, and a third of those are cancer [0]. Globally, 31% of men and 6% of women smoke daily. 17% of Americans are daily smokers. Over 1 billion people are projected to die due to tobacco-related illnesses in the 21st century.
(2) Obesity: A recent epidemiological study found that 4% of cancer in men and 7% in women was due to obesity. It was as high as 40% for some cancers such as endometrial and esophageal adenocarcinoma [1].
(3) Alcohol/Red & Processed Meat: Consumption of alcoholic beverages is a known human carcinogen. A recent study estimated that 3.5% of all cancer deaths can be attributed to alcohol [2]. A separate study found that 3% of all cancers, including 21% of bowel cancers, was attributed to red & processed meats [3].
(4) Environmental & Occupational Hazards: The WHO estimates 19% of all cancers globally are attributable to environmental factors [4]. This includes air pollution, which likely causes 3% to 14% of all lung cancers, as well as exposure to chemicals in the workplace such as asbestos.
[0] http://www.ncbi.nlm.nih.gov/books/NBK54023/
[1] http://www.cancer.gov/about-cancer/causes-prevention/risk/ob...
[2] http://www.cancer.gov/about-cancer/causes-prevention/risk/al...
[3] http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/...
The logistics are not the same with cancer preventing drugs at all.
And we've already been looking for cancer drugs for more than half a century to know that the logistics compared to vaccines are different. Let's put it this way: if they knew of a method to make cancer prevention drugs as easy and effective as vaccines, they'd have made them.
Also vaccination is one of the most logistically complicated processes in medicine they are extremely short lived require very precise refrigeration and proper administration is considerably more critical than most cancer treatments, 80-90% of the cost of vaccination programs in developed and developing countries alike go into logistics. For cancer treatments even the experimental highly specialized ones it's completely the opposite, and run of the mill treatments like chemotherapy are easily administered by medical technicians under almost any circumstances.
All of that is known, and they've been trying that for half a century with not much success (besides the occasional report for a "cancer vaccine"). What makes you think they don't know the logistics involved already?
>Also vaccination is one of the most logistically complicated processes in medicine they are extremely short lived require very precise refrigeration and proper administration is considerably more critical than most cancer treatments, 80-90% of the cost of vaccination programs in developed and developing countries alike go into logistics.
Not really relevant. Being short lived and requiring "precise refrigeration and proper administration", is not the same kind of problem as the research for cancer vaccines.
The former is actually a solved problem, and something that even all third world countries are able to do just fine anyway...
No it hasn't tumor antigens are a fairly recent discovery, the epigenetics of cancer as well as it's relationship with the immune system are also quite new fields. MUC1 was only discovered in the mid 80's it's expression initially linked to cancer in the mid 90's since the mid to late 2000's where we actually started trialing this out and started developing immunologic therapeutic processes. If we are talking about cancer specific therapeutic vaccines then there are already several on the market some of which are classified as orphan drugs and can be sponsored most of them are currently only life prolonging treatments for cancers with no other treatment course.
And again it's not like overall vaccination is a closed book there are only a handful of diseases we can effectively vaccinate against and those are ones which are immune system is pretty damn good in dealing with the begin with.
I really don't understand your argument anymore because at this point you are arguing about the logistics of vaccinating against chickenpox vs developing new cancer treatments which is asinine. New research is done everyday doesn't matter if it's into vaccines for new viral diseases or cancer the logistics of the research are the same. And if you are talking about delivery logistic than cancer would win every blood day of the week.
http://www.mayoclinic.org/healthy-lifestyle/sexual-health/in-depth/cervical-cancer-vaccine/art-20047292And if it was you do realize that you are only proving my point right?
I know there are many causes for cancer, but there are also potential anti cancer (note anti cancer not cancer causes) vaccines as your body does develop cancer specific antigens.
The problem is that your immune system is too slow to react that that tumors have specific mechanisms that are intended to evade it (colloquially known as tumor escape mechanisms), there are quite a few generic therapeutic cancer vaccines in development like Stimuvax and Imucin both targeting various antigen mechanisms like MUC1[0].
But again this is "proving my point" as the OP claimed there cancer treatment and vaccination isn't comparable, as there are no wide spread vaccines on the market atm but they are a very promising area of study it's not the case.