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Why haven't we cured cancer yet?

sciencebasedmedicine.org

111–120 of 167 posts

Re: Why haven't we cured cancer yet?

#111

Very interesting read... it boggles my mind how complex our organisms are and how cancer forms and takes everything over from the inside. We can't even "cure" a relatively simple virus like the cold or influenza, and cancer is like 10,000x times more complicated - gotta respect all the hackers who're working in the medical field...

I had more appreciation for the complexity of the human organism after reading this NYTimes article about our microbiome: http://www.nytimes.com/2010/07/13/science/13micro.html?_r=1&...

10 times more microbial than 'human' DNA in our body.

Re: Why haven't we cured cancer yet?

#112

Earlier quoted context omitted.

> But if you do this for enough billionaires, the common elements in the problem will start repeating and the researchers will learn a repertoire of common hacks. No, they'll at best learn nothing, or more likely think they learn something and send the entire field off into the woods for a decade or two. Crack open "the Emporer of all Maladies" for a glimpse at just how difficult it is to judge effectiveness of treat…

just how difficult it is to judge effectiveness of treatments and preventions in even extremely controlled studies. Translation: "just how difficult it is to be absolutely absolutely absolutely * 10^7 sure we're not selling quack medicine." The treatment of Steveoma is effective if Steve gets better. If not, it isn't. The sample size is 1 by definition. Obviously, if Steve gets better and he's taking 30 drugs, no one…

>The treatment of Steveoma is effective if Steve gets better. If not, it isn't. The sample size is 1 by definition.

Well, it's effective if Steve gets better than he would have if he hadn't taken it. That's a rather important distinction, and it's real hard to tell the difference with low sample sizes.

Re: Why haven't we cured cancer yet?

#113

Earlier quoted context omitted.

> But if you do this for enough billionaires, the common elements in the problem will start repeating and the researchers will learn a repertoire of common hacks. No, they'll at best learn nothing, or more likely think they learn something and send the entire field off into the woods for a decade or two. Crack open "the Emporer of all Maladies" for a glimpse at just how difficult it is to judge effectiveness of treat…

just how difficult it is to judge effectiveness of treatments and preventions in even extremely controlled studies. Translation: "just how difficult it is to be absolutely absolutely absolutely * 10^7 sure we're not selling quack medicine." The treatment of Steveoma is effective if Steve gets better. If not, it isn't. The sample size is 1 by definition. Obviously, if Steve gets better and he's taking 30 drugs, no one…

I understand where your ideas come from, I wish they were true. But sadly they are misinformed on many levels, and the root of the problem is you are playing a statistical game where reality will win.

- There are not enough Billionaires to meet your needs, statistically you'll need quite a few to find any decent cures. Especially with 30 teams in play on each case; figuring out "what worked" is a bad numbers game in that case.

- Science shows there is unlikely to be one "magic bullet" for cancer, which makes it hard to cure individuals and then take that science into a wider populace; "something here worked, but does it work generally?"

- Cancer treatments are harsh and invasive - by design! 30-40 competing drugs is unsustainable, you would be, to put it mildly, royally fucked. So death could come simply by exhausting the body with treatment, as easily as anything else.

- You invoked Godwin's law, which is never a good sign.

I agree with your general premise; which is that it takes too long to iterate ideas into actual production. But the reason that scenario exists is not just "quack medicine" and other hopeful (but useless) remedies, it is for the case of "oh shit, I just killed a million people because we didn't investigate long term effects".

And that is where your theory really fails; because you are trading an unknown collateral now, for an unknown collateral in the future. I'm not arguing against either as a good or bad thing; but it does highlight the fatal flaw in the argument "you are killing X people right now by not releasing/iterating fast enough"

Re: Why haven't we cured cancer yet?

#114
The part that jumped out at me was this: "for most solid tumors the time from founder mutation to clinically apparent metastasis is between 20 and 30 years"

If cancer is really this ultimate chimearan opponent, why don't we put more emphasis on detecting it during the twenty years before it becomes dangerous?

It would be difficult to detect changes at the cellular level at any location in the human body. But it sounds like a problem that will scale with "Big Data" a lot better than trying to fight evolution.

Re: Why haven't we cured cancer yet?

#115
post #98

Earlier quoted context omitted.

I'm going to be a heretic and argue that the problem with cancer research is institutional, not biological. The biological problem is clearly very hard, but the institutional problem is impossible. You might or might not be familiar with the term "OODA loop," originally developed by fighter pilots: http://en.wikipedia.org/wiki/OODA_loop If the war on cancer was a dogfight, you'd need an order from the President every…

[There's a TL/DR at the bottom] Everyone's cancer is its own disease (if not several), so the researchers are fighting one disease (or several), instead of an infinite family of diseases. They are not trying to cure pancreatic cancer - they are trying to cure Steveoma. You're absolutely right that this is the mentality that future treatments need to take. In terms of treatment response, a liver tumour could have far…

You're absolutely right that this is the mentality that future treatments need to take.

Yeah, and I'm sure our regulatory infrastructure will catch up sometime in the Obama administration. That is, the Malia Obama administration...

If this time frame were possible this would be ideal, however, unfortunately each of these steps (if they are possible) takes significantly longer than an evening, and typically far longer than a patient has.

Then speed them up! You might have heard the story of Steve and Gorilla Glass:

http://en.wikipedia.org/wiki/Gorilla_Glass

You're not going to tell me the actual chemical reactions are slow. It's all human labor. The speed of any organization is limited by the schedule on which results are demanded - compare the Manhattan Project to the new Bay Bridge.

This is a risky game. How do I (the scientist) know which drugs were effective? How do I know how they'll react with one another? If my focus is Steve, then do I really want to risk killing him through an unexpected cross reaction of my 30-40 untested drugs?

Yes, because Steve knows he's at risk of dying anyway. Being an intelligent person, Steve compares the risk of dying from neglect, versus dying from treatment, as apples to apples. Do you?

There are (apparently) 1210 billionairs in the world. So say they all get cancer and get this team of doctors - if any of the patients survive then some aspect of the treatment worked. If they don't some aspect failed. It would be impossible to determine which is which.

It would be impossible to determine which is which by the present statistical standards. Ie, it would be impossible to absolutely absolutely 10^7 know which was which. It might be possible for an intelligent person to make a good guess, however.

This is how technique advances in any technical field that can't be reduced to pure mathematics. If you're limited to advancing on the basis of perfect truth that absolutely * 10^7 knows it's right (even if when tested in practice, it's 90% irreproducible), you can barely advance at all. Guess what - we're barely advancing at all.

A combined focus of translational and basic research is essential, with a frequent and effective dialogue between the two.

The best way to have a frequent and effective dialogue is to make basic researchers part of the teams treating patients. The distinction is imaginary, anyway.

This was I believe the case for Steve, but not even for Steve could they do personalized drug development as described. They couldn't even try drug candidates which other developers and/or researchers had abandoned along the way - an enormous library of molecules, if properly collated.

Ultimately, your argument assumes the rate of discovery will be constant. You need to consider the research in the broader picture. Cancer is a genetic disease (in terms of pathological origin, not necessarily in hereditary terms). It cost the (publicly funded) human genome project $3bn to sequence a human genome in about 12 years. Now it costs $5000 in a week or so, and both the cost and the time is coming down.

It's a separate discussion, but you're actually making the argument against investing in basic cancer biology. Rather, all the investment should be in sequencers, etc.

Reason: consider the studies you did with the tools of 10 years ago. What was difficult then is trivial now. So in what way did it contribute to what you know now? In no way, which makes it useless - if you hadn't done the work then, expensively, you could do it now, trivially. Now, consider the studies you'll do with the tools of 10 years from now...

Of course, the practical effect of funding cancer biology is to fund tools development. But it's a somewhat indirect way to accomplish the objective...

Re: Why haven't we cured cancer yet?

#116
post #95

Earlier quoted context omitted.

Big drug companies are CONSTANTLY exploring new areas, trust me, they looked into DCA and found it wanting. I can't personally attest to the amount of R&D dollars spent by pharma on R&D, but it has been EXTENSIVELY studied, just checked out pubmed (gov't funded research). http://www.ncbi.nlm.nih.gov/pubmed?term=dichloroacetate If DCA were an effective agent, they would have handed the U of A a handsome check for that…

Hundreds of millions of dollars and years of clinical trials are needed to prove if DCA is effective or not. You can't just say "trust me, they looked into DCA and found it wanting". Looked at it how? Have they done years of clinical trials? did they spend millions in R&D on this?

There have been small clinical trials of DCA conducted already. That data is out. They were not compelling enough to warrant the type of investment you are talking about (multi-year clinical trials).

That's not to say it may not be found effective for some types of cancers in the future. But what it does tell us is that the lack of interest in spending more money on r&d is not some conspiracy by pharma because they can't make money on it, rather, it's because the data just hasn't been that impressive so far.

Re: Why haven't we cured cancer yet?

#117

The National Cancer Institute's average yearly budget for cancer research is around $4.9 billion. NFL football revenue? $9 billion. Priorities.

Although I understand your point, there is a limit to the rate in which you can even spend cancer research money, even if you wanted to dramatically increase it. For one thing, you are limited to funding the research that you think will lead to a cure. It may turn out that the level of funding for direct cancer research is fine but what is needed is increased funding for nano-robotics or strong AI, or supercomputers that can simulate tumor growth and evolution. The linked article was very sobering indeed; finding a cure for cancer almost seems like trying to find a grand unified theory for physics. It may turn out that you basically have to figure out how to cure all diseases in order to cure cancer.

Re: Why haven't we cured cancer yet?

#118
It seems like there needs to be a combination of cultural/societal changes favoring education in the life sciences, combined with funding. The launch of Sputnik led to an upsurge of focus in math and science education during the Cold War. To a much smaller degree, C.S.I. inspired a generation of forensic scientists.

Maybe the startup response to this piece should be to figure out ways to spark public interest in tackling this problems.

Re: Why haven't we cured cancer yet?

#119

Earlier quoted context omitted.

just how difficult it is to judge effectiveness of treatments and preventions in even extremely controlled studies. Translation: "just how difficult it is to be absolutely absolutely absolutely * 10^7 sure we're not selling quack medicine." The treatment of Steveoma is effective if Steve gets better. If not, it isn't. The sample size is 1 by definition. Obviously, if Steve gets better and he's taking 30 drugs, no one…

I understand where your ideas come from, I wish they were true. But sadly they are misinformed on many levels, and the root of the problem is you are playing a statistical game where reality will win. - There are not enough Billionaires to meet your needs, statistically you'll need quite a few to find any decent cures. Especially with 30 teams in play on each case; figuring out "what worked" is a bad numbers game in…

I have some questions about your points... How many people do you think one would need to find any decent cures/treatments? How many patients are current researchers making use of to accomplish the feat? If moldbug had said something along the lines of "you can increase the numbers by having billionaires fund people other than themselves, such as their parents or other people they care about, or just as donations, in ways that don't bankrupt them but still provide lots of experimental data", do you think the increased number could still not possibly be enough, would you still object?

If moldbug had started with 5 concurrent treatments instead of 30, would you object to that? (Though considering death is coming I personally would rather die of treatment exhaustion from X treatments than the actual cancer, knowing I tried many potential solutions. (This conditional on a cancer that actually threatens my life.))

Lastly, are the "unknown collaterals" equivalent unknowns? Shouldn't we try to estimate them and decide whether ramping up the release/iterate process is worth it? That people are dying because the research system sucks doesn't seem that controversial to me or very unknown in truth-value. How likely do you think it is that someone kills 1 million people with some remedy, and how likely do you think it is that the same 1 million people would have lived much longer without such a remedy being attempted on them?

Re: Why haven't we cured cancer yet?

#120
post #97

Earlier quoted context omitted.

You are right. I did not mean that sequencing shouldn't be done, what I meant was that the simple idea of sequence -> nearest match -> most appropriate treatment won't work due to the massive amount of variance involved. So the sequencing will be more useful at higher level. So more understanding patterns and devising strategies than personalizing cocktails.

Ah, I see what you're saying. Though even going with the best treatment in the nearest match is a huge leap forward over what we can currently do. I see two ways forward, using the current class of chemotherapeutics + small molecule/antibody targetted therapies. As straw men, they are: 1) come up with a totally complete model of what everything in the cell does, how the mutations affect those interactions amongst gen…

I think Moore's law can help to an extent with approach 1, especially the protein folding bottleneck. We also need better computational techniques, taking more from dynamical systems maths for example.

I think approach 2 can also inform approach 1. Especially if grey and clearbox models are used - probabilistic graphical models, markov logic networks even genetic programming. So instead of using them for just prediction or a distance metric, we study the patterns in the models they produce. For example, instead of merely fitting a bunch of weights in some sum product model, one could use genetic programming where the primitives represented actual computations from a simplified model of cell dynamics. So while not guidance it still offers some way of embedding some intelligence in the search.

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