9 ms·
Why Is It So Difficult to Develop Drugs for Cancer? (2010)
- iskander 11y agoIt's amazing to read an article about cancer drug development which doesn't talk about the successful immunotherapies. I know that checkpoint blockade and cellular therapies weren't as widely known in 2010, but it shows how shockingly far research has moved in a relatively short period of time.
- venomsnake 11y agoYou will be surprised how fast research can move when the generation holding the power are nearing their old age
- iskander 11y agoThat's been true as long as treatments for cancer have ever been researched (reaching back to the 1800s). Only recently have immunotherapies started yielding significant clinical results for common cancer types. I think the change in efficacy has a lot more to do with the accumulation of scientific knowledge about the immune system (it hasn't been long since we even discovered T-cells or dendritic cells), along with huge improvements in genetic sequence & editing.
- venomsnake 11y agoYeah but baby boomers are and exceptional generation. The generation behind them is smaller (the Gen-X ers)
- melling 11y agoHow ignorant are you? Generations of rich and powerful people have been dying for quite some time.
- hugh4 11y agoIt seems to be the shared assumption of the Internet age that somewhere out there is a powerful "them" controlling everything. All the worlds problems are due to "them" acting in their own interests, and everything would be fine if only "we" could put ourselves in charge instead.
- venomsnake 11y agoBaby boomers do hold position of power and a lot of wealth. There are also lots of them.
- dang 11y ago> How ignorant are you? No personal attacks, please. This comment would be fine with just the second sentence.
- BorisMelnik 11y agoVery informative, is there some sort of 2015 updated version of this to show how far we've come in regards to the Kaplan-Meier curve?
- astazangasta 11y agoCurves differ by disease. There is no "cancer", just a host of related diseases that each require their own therapy.
- iskander 11y agoThe biggest difference, as of 2015, is that we now have an extremely promising and more coherent research direction in the form of immunotherapy: (1) activating and disinhibiting adaptive immune cells (2) engineering highly active immune cells that target known tumor markers, and mostly recently, (3) personalized therapeutic vaccination against a patient's specific cancer. The first two approaches have already shown significant improvements in survival for several cancer types and there are literally hundreds, if not thousands, of combinations and variations worth trying that might extend efficacy to most cancer types. Specifically, for metastatic melanoma, the "asymptote" of trial survival curves used to be around 0-10% long-term survivors. The first successful immune checkpoint agent, ipilimumab, brought the survival asymptote up to ~15-20%. The next agents, nivolumab & pembrolizumab, brought the survival asymptote up to ~40-60%. The combination of both approaches seems to result in long-term survival for ~60-85% of patients (at the cost of more extreme side effects). That's a tremendous improvement that we've seen over just ~8 years, and in a disease that was previously thought to be intractable.
- iskander 11y agoThe article is paywalled for me, is there an alternative link?
- alephnil 11y agoThere are several reasons why cancer is so difficult to treat, but the main one is simply that cancer cells is the patients own cells that have a couple of mutations, so most things that kill cancer cells also kill healthy cells. Thus successful cancer treatments are those who kills the cancer cells, but only almost kill the patient. The other main reason why cancer treatment is difficult is that there are many different combinations of genes that can mutate and cause cancer, so that even the same cell type can get cancer several different ways. There are at least six different kinds of breast cancer for example, where a drug effective against one can be totally ineffective against another, and this is the case for a lot of cancer types. Thus cancer is not one decease, but hundreds of different deceases, each requiring different treatment. It is quite amazing that more than half of those getting cancer treatment actually get cured today.
- raarts 11y agoSpelling 'disease' correctly would add a lot of credibility to your arguments.
- Myrth 11y agoA question for people in the know - if there's a research/treatment that can not be patented/monetized due to its generic nature, but it still requires millions of dollars in trials - is it doomed to never be done?
- refurb 11y agoI would say a real breakthrough would still get done through gov't or non-profit support. It just might take a lot longer than a drug with clear financial upside. DCA - dichloroactate comes to mind. It was promising but unpatentable. It got lots of funding.
- atomical 11y agoThere are a lot of research chemicals that have potential but are discarded for various reason. Usually the reasons revolve around efficacy. A lot of them can be bought off Alibaba. Something to think about if you're desperate. Myo-inositol trispyrophosphate has a lot of potential for cancer treatment. And its use in sports doping has decreased the price.
- J_Darnley 11y agoHeh. What I read there is "Even more widespread doping is sports will lead to a cure for cancer". Sounds like a reason to encourage doping rather than trying to stamp it out.
- deleted 11y ago[deleted]
- carbocation 11y agoUnless the therapy you envision requires simply isolation of unchanged DNA and injection of that DNA back into a person without any modification whatsoever, it's likely that you could obtain a patent on a novel therapy.
- dnautics 11y agoI think that not too many folks have tried that hard, really. But whatever, I'm giving it a shot. (Setting up and running a fun experiment today). I got 60k in funding from crowd funding, which is great for a startup nonprofit with no reputation. This is enough to do a mouse equivalent of the kaplan-meier curve.... But not enough to pay myself (I variously drive for Lyft and contract code to make ends meet). Worth noting the salk and Sabin polio vaccines were not patented.
- static_noise 11y agoTwo things come to mind immediately: 1. Cancer cells are human cells and behave very similar to human cells compared to foreign bacteria or viruses which have a vastly different metabolism. 2. Cancer is not a single disease but a gazillion different mutations which may have vastly different characteristics. Point 1 most of the time prevents cures such as "kill the human cells" from working effectively without killing the patient, too. Successufull cancer cells look so "human" that even the immune system doesn't see the difference. Point 2 means that the "cure for cancer" may be found for some kinds of cancer but there are thousands more. If we cure all cancers known today we will find new ones when the patients are just a few years older. Remember that the death rate increases exponentially with age and so will diseases like cancer.
- agumonkey 11y agoRecent articles about tumor growth heterogeneity : http://www.nature.com/nature/journal/v525/n7568/full/nature14971.html http://www.nature.com/nature/journal/v525/n7568/full/nature1... Videos below are pretty telling.
- mehrzad 11y agoDo you study biochemistry or medicine? Because it would seem that your first point is completely true but technically an oversimplification when it comes to treatment of common cancers. https://en.wikipedia.org/wiki/Asparaginase#As_a_drug https://en.wikipedia.org/wiki/Asparaginase#As_a_drug https://en.wikipedia.org/wiki/Bcr-Abl_tyrosine-kinase_inhibitor https://en.wikipedia.org/wiki/Bcr-Abl_tyrosine-kinase_inhibi...
- suchire 11y agoThose are classic success stories mainly because they were the low-hanging fruit for targeted cancer treatment. For blood-cell cancers like leukemia and lymphoma, treatment has come a long way due to advances like the ones you mentioned. For "solid" tumor cancers like breast, pancreatic, prostate, and skin cancer, we're still struggling to make a dent in the death rate.
- nextos 11y agoI think much progress will come in the form of early diagnostics. It's easy to spot developing cancers by looking for free DNA in blood. Cheap and non-invasive.
- DanBC 11y agoHow do you tell the difference between slow growing cancers and fast growing cancers? EG: for many men the treatment for prostate cancer has severe side effects and their cancer is something they would have died with, not of. Being able tell which cancers are slow or fast would improve many lives.
- iskander 11y agoOne idea: if you have a biomarker you can track via CTCs or ctDNA, then you could watch the rate at which that marker's availability increases. The PSA doubling time for indolent prostate cancers can often be measured in years, whereas CA 19-9 doubling time for pancreatic cancer is more often measured in days or months.
- iskander 11y agoThis works particularly well for cancers with recurring mutational patterns (like KRAS mutations in pancreatic cancer), since that lets you affordably do ultra-deep sequencing of small regions of the genome. If you had to deep (>5000x coverage) sequencing of many megabases then (with currently available platforms) the diagnostic wouldn't be affordable.
- easter6 11y agoearly detection is great, if you're being specifically checked for cancer. the problem is that you can have tumors growing inside you for years, and during that time, the effects of those tumors may lead your doctor to misdiagnose the problem. And by the time those tumors make themselves painfully obvious, you've got Stage 4 cancer which is pretty much a death sentence. In the US you can order your doctor to arrange a cancer screening for you (scan or blood test), if you are worried you may have cancer. It's your money, after all. In other countries such as Canada, that's not so easily done. You're at the mercy of whatever doctor you've ended up with, and that doctor is not going to do anything for you unless it makes sense to him. This has basically been my experience, anyhow. Thanks to my doctor's inaction I have maybe 6 months to live.
- pvnick 11y agoThis is the kind of statistics that really tugs at your heart strings. This is a Kaplan–Meier chart: http://oncology101.net/wp-content/uploads/2013/04/OPTMAL_survival-curve1.jpg http://oncology101.net/wp-content/uploads/2013/04/OPTMAL_sur... Everytime the line takes a step down, at least one person has died. The only happy ending is that less people die, and a really happy ending is when significantly less people die in the treatment group than the control group. Really puts things into perspective.
- Tegaves1969 11y agoI've made $96,000 so far this year working online and I'm a full time student. Im using an online business opportunity I heard about and I've made such great money. It's really user friendly and I'm just so happy that I found out about it. Heres what I do...www.Buzz34.Com
- danieltillett 11y agoCancer is hard for lots of reasons, but the main reason we have not made the progress we should have is the way we are going about looking for new treatments. Our animal models don't reflect natural human disease, we use the wrong way of classifying cancers (by tissue of origin rather than sensitivity), and we require that all new treatment provide a rapid response in terminal patients (stage I/II trials). If you made me cancer dictator with an NIH sized budget and an ability to set the rules I could provide very rapid progress. Edit. I normally don't care about being down voted, but on a serious topic like this it really does everyone a disservice. If you disagree with something I have written then please reply rather than mindless reaching for the down arrow.
- iskander 11y ago>If you made me cancer dictator with an NIH budget and an ability to set the rules I could provide very rapid progress. What would you change?
- danieltillett 11y agoThis is really deserving of a blog post/essay, but the main thing to get right is the discovery process. We have millions of pre-existing drugs (the NIH has looked at millions on its own), the problem is the way we go about selecting possible treatments from them. In brief what I would do is: 1. Demand we use animal models that reflect actual human disease (natural occurrence in old age). No more sticking human cancers cell lines into SCID mice. 2. Genome sequence all human cancers so that we classify them by genetic defects. We should not care which tissue a cancer arose in, but by which drugs it is selectively sensitive to. 3. Test new treatments in patients that reflect actual patients - ie newly diagnosed patients, not patients that are weeks away from dying and who have failed everything else. 4. Go all out on the immune approach with an emphasis on developing treatments with minimal side-effects that can be given to healthy people as a preventative treatment. We need to think about cancer as something we prevent rather than cure.
- iskander 11y ago
- Eric_WVGG 11y agoThis comic is a pretty great summation: http://www.phdcomics.com/comics/archive.php?comicid=1162 http://www.phdcomics.com/comics/archive.php?comicid=1162
- JesperRavn 11y agoI especially like how it explains the meaning behind the oft repeated mantra that cancer is not a single disease, or that cancer is not a single disease therefore there will never be a cure for cancer. Both these statements reflect true facts about the nature of cancer, but out of context they sound like weird illogical platitudes.
- giardini 11y agoUnfortunately the comic missed the reason why such research continues: people will pay most of their money for a cure for (or even a temporary reprieve from) _their_ cancer. This becomes "all of their money" rather than "most..." if their child has cancer. Cancer centers are enormous money-generating systems. Most of their research is useless but the doctors running them get rich, the corporations who own them get rich, all of their patients die and in the end nobody cares so the process continues.
- iskander 11y agoI actually agree with you up until the last sentence. Many researchers and doctors care quite a bit and are excited to finally be moving toward curative treatments (rather than chemo treadmills).
- deleted 11y ago[deleted]
- mhkool 11y agoIf you have seen the documentary about the work of Dr Burzynski, then you already know why there is not yet an official cure for cancer. In a nutshell: the industry and the US cancer foundation are corrupt. I am sure that many do not believe what I say because "it cannot be true". But read http://www.burzynskipatientgroup.org/ http://www.burzynskipatientgroup.org/ and watch the documentary https://www.youtube.com/watch?v=rBUGVkmmwbk https://www.youtube.com/watch?v=rBUGVkmmwbk and decide for yourself. And there are many "alternative" treatments that cure cancer. One of the oldest and most famous is the Gerson Therapy.
- blazespin 11y agocancer is the halting problem: https://en.wikipedia.org/wiki/Halting_problem https://en.wikipedia.org/wiki/Halting_problem
- danieltillett 11y agoNo need to be that pessimistic.
- reasonattlm 11y agoI'd argue that progress is slow because the research community is spending too little time on lines of work that can address many or all types of cancer. If you look at most cancer research it is highly specific to the molecular biochemistry of one subtype of cancer with a tiny percentage of overall patients. Yet that work is rarely any less costly than any of the possible paths forward to broad cancer therapies. Examples: 1) Telomere extension interdiction, either via disabling telomerase in some way, or more cleverly disabling the effects of telomerase in a targeted fashion in cancer cells only, as has been demonstrated in early stage research. 2) ALT disruption, for the minority of cancers that abuse ALT to extend telomeres rather than telomerase. 3) Chimeric antibody receptor based immunotherapies. Still to soon to tell how broad these might be in their application. 4) CD47 targeting coupled to any discriminating cell destruction system. CD47 seems to be a very broad marker for many types of cancer. But disruption of telomere lengthening is definitely at the top of this list. It should be possible to suppress it globally (both telomerase and ALT) in a patient in the worst case and wait out the cancer's withering before turning it back on. This would be considerably less harmful than chemotherapy and much more effective. It would require no targeting, no cancer specificity, and just work. A number of research groups are working on slices of this technology, but by no means enough.
- mmaunder 11y agoA few comments: Firstly early detection has gotten way better than the 90's. PET/CT's are standard in the USA now which is awesome for staging and diagnostics - still scarce in the rest of the World. Early diagnosis is huge in treating the big C. Drugs that aren't chemotherapy but are biotherapies (or immunotherapies) like Rituximab (Rituxin) are available now which have improved prognosis in some cancers by 15% which is a big deal. Pathology labs are doing a much better job now of identifying genetic subtypes which help target therapies. Right now they use staining techniques to figure out which subtype you have based on a known subtype looking the same way when stained. Hopefully one day they'll be able to sequence each pathology sample. Also just responding to a few comments about the economics: Cancer drugs and treatment are insanely expensive in the USA and much of the rest of the World. So the economic incentive is very much there for companies like Genentech to develop drugs like Rituxin (at $5K a dose). So my sense is that this isn't a cure or no cure disease. Instead we're accelerating towards improving outcomes by either putting the disease into remission in a lot of patients and delivering in some cases decades more life - or actually curing them.
- zmmmmm 11y agoHonestly, 2010 is now quite a long time ago in cancer research. I would not read any article from then and hope to understand the current state of knowledge. Not that it isn't interesting, but it's almost more from a historical perspective at this point.
- Gatsky 11y agoI don't believe that the answer to this is "because the task is difficult". I actually think the answer is simply - because the life sciences are in their infancy. It's like asking a medieval astronomer why it's so difficult to fly to the moon. At the end of the day we do science with our brains, and our brains are not built to understand biology. How could they be? To really be able to understand even the simplest, isolated biological process, you probably need to hold at least a thousand bits of data in working memory. You can build a model on a computer, but we still don't know what the important bits of data are out of many millions, we don't know when they are missing, and we don't know when our model begins to be valid and ceases to be valid. In contrast, a physicist can gain deep insight about the ENTIRE universe while sitting under a tree with a pen and paper and some cogent abstractions. Furthermore, this insight is valid backwards and forwards in time except in clearly obvious extreme conditions. This is actually completely amazing when you think about it. We would like to think the same about biology, and scientists act this way, but we would be mistaken. Abstractions fail in biology. Even the most basic and obvious abstractions made by humans, like the concept of a gene, are too simple to act as a foundation for ongoing discovery. And we don't have any alternative framework.
- known 11y agoEditing DNA should cure Cancer; http://www.bbc.com/news/health-34200029 http://www.bbc.com/news/health-34200029