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Why Is It So Difficult to Develop Drugs for Cancer? (2010)

63 pointsby valhallaover 9 years ago

16 comments

static_noiseover 9 years ago
Two things come to mind immediately:<p>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.<p>2. Cancer is not a single disease but a gazillion different mutations which may have vastly different characteristics.<p>Point 1 most of the time prevents cures such as &quot;kill the human cells&quot; from working effectively without killing the patient, too. Successufull cancer cells look so &quot;human&quot; that even the immune system doesn&#x27;t see the difference. Point 2 means that the &quot;cure for cancer&quot; 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.
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pvnickover 9 years ago
This is the kind of statistics that really tugs at your heart strings. This is a Kaplan–Meier chart: <a href="http:&#x2F;&#x2F;oncology101.net&#x2F;wp-content&#x2F;uploads&#x2F;2013&#x2F;04&#x2F;OPTMAL_survival-curve1.jpg" rel="nofollow">http:&#x2F;&#x2F;oncology101.net&#x2F;wp-content&#x2F;uploads&#x2F;2013&#x2F;04&#x2F;OPTMAL_sur...</a><p>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.
Eric_WVGGover 9 years ago
This comic is a pretty great summation: <a href="http:&#x2F;&#x2F;www.phdcomics.com&#x2F;comics&#x2F;archive.php?comicid=1162" rel="nofollow">http:&#x2F;&#x2F;www.phdcomics.com&#x2F;comics&#x2F;archive.php?comicid=1162</a>
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reasonattlmover 9 years ago
I&#x27;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.<p>Examples:<p>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.<p>2) ALT disruption, for the minority of cancers that abuse ALT to extend telomeres rather than telomerase.<p>3) Chimeric antibody receptor based immunotherapies. Still to soon to tell how broad these might be in their application.<p>4) CD47 targeting coupled to any discriminating cell destruction system. CD47 seems to be a very broad marker for many types of cancer.<p>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&#x27;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.
mmaunderover 9 years ago
A few comments: Firstly early detection has gotten way better than the 90&#x27;s. PET&#x2F;CT&#x27;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.<p>Drugs that aren&#x27;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.<p>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&#x27;ll be able to sequence each pathology sample.<p>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).<p>So my sense is that this isn&#x27;t a cure or no cure disease. Instead we&#x27;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.
BorisMelnikover 9 years ago
Very informative, is there some sort of 2015 updated version of this to show how far we&#x27;ve come in regards to the Kaplan-Meier curve?
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Myrthover 9 years ago
A question for people in the know - if there&#x27;s a research&#x2F;treatment that can not be patented&#x2F;monetized due to its generic nature, but it still requires millions of dollars in trials - is it doomed to never be done?
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Gatskyover 9 years ago
I don&#x27;t believe that the answer to this is &quot;because the task is difficult&quot;. I actually think the answer is simply - because the life sciences are in their infancy. It&#x27;s like asking a medieval astronomer why it&#x27;s so difficult to fly to the moon.<p>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&#x27;t know what the important bits of data are out of many millions, we don&#x27;t know when they are missing, and we don&#x27;t know when our model begins to be valid and ceases to be valid.<p>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.<p>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&#x27;t have any alternative framework.
alephnilover 9 years ago
There 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.<p>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.
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iskanderover 9 years ago
It&#x27;s amazing to read an article about cancer drug development which <i>doesn&#x27;t</i> talk about the successful immunotherapies. I know that checkpoint blockade and cellular therapies weren&#x27;t as widely known in 2010, but it shows how shockingly far research has moved in a relatively short period of time.
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knownover 9 years ago
Editing DNA should cure Cancer; <a href="http:&#x2F;&#x2F;www.bbc.com&#x2F;news&#x2F;health-34200029" rel="nofollow">http:&#x2F;&#x2F;www.bbc.com&#x2F;news&#x2F;health-34200029</a>
nextosover 9 years ago
I think much progress will come in the form of early diagnostics. It&#x27;s easy to spot developing cancers by looking for free DNA in blood. Cheap and non-invasive.
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zmmmmmover 9 years ago
Honestly, 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&#x27;t interesting, but it&#x27;s almost more from a historical perspective at this point.
blazespinover 9 years ago
cancer is the halting problem: <a href="https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Halting_problem" rel="nofollow">https:&#x2F;&#x2F;en.wikipedia.org&#x2F;wiki&#x2F;Halting_problem</a>
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iskanderover 9 years ago
The article is paywalled for me, is there an alternative link?
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danieltillettover 9 years ago
Cancer 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&#x27;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&#x2F;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.<p>Edit. I normally don&#x27;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.
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