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 time you wanted to adjust your ailerons. Your OODA loop is 10-20 years long. If you're in an F-16 with Sidewinder missiles, and I'm in a Wright Flyer with a Colt .45, I'm still going to kill you under these conditions. Cancer is not (usually) a Wright Flyer with a Colt .45.

Lots of programmers are reading this. Here's an example of what life as a programmer would be like if you had to work with a 10-year OODA loop. You write an OS, complete with documentation and test suites, on paper. 10 years later, the code is finally typed in and you see if the test suites run. If bug - your OS failed! Restart the loop. I think it's pretty obvious that given these institutional constraints, we'd still be running CP/M. Oncology is still running CP/M.

Most cancer researchers are not even in the loop, really. For one thing, 90% of your research is irreproducible:

http://www.pharmalot.com/2012/03/many-cancer-studies-are-act...

Even when the science is reproducible, your cell lines and mouse models are crap and bear little or no resemblance to real tumors. You know this, of course. But you keep on banging your heads against the wall.

What would a tight OODA loop look like? Imagine I'm Steve Jobs, with infinite money, and I have cancer. 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.

Second, they operate with no rules. They can find an exploit in Steve's cancer genome on Wednesday, design a molecule to hack it on Thursday, synthesize it on Friday and start titrating it into the patient on Saturday. Pharmacokinetics? Just keep doubling the dose until the patient feels side effects. Hey, it worked for Alexander Shulgin.

Moreover, Steve isn't on just one drug. He's got thirty or forty teams attacking every vulnerability, theoretical or practical, that may exist in his cancer cells. Why shouldn't he be attacking his cancer in 30 ways at the same time? He's a billionaire, after all.

Not everyone is a billionaire. 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. Eventually, the unusual becomes usual - and cheap. This is the way all technology is developed.

Of course, someone might screw up and a patient might die. You'll note that a lot of cancer patients die anyway. Steve got a lot, but he didn't get this - why not? It would be illegal, that's why. Sounds like something the Nazis would do. Nazis! In our hospitals! Oh noes!

The entire thrust of our medical regulatory system, from the Flexner Report to today, is the belief that it's better for 1000 patients to die of neglect, than 1 from quackery. Until this irrational fear of quack medicine is cured, there will be no real progress in the field.

The entire process we call "drug development" is an attempt to gain six-sigma confidence that we are not practicing quack medicine. Especially for cancer, do we need all these sigmas? And are we obtaining them in an efficient way? I can't imagine how anyone would even begin to argue the point.

What is the source of this phobia? It is ultimately a political fear - based on public opinion. Its root is in the morbid, irrational fear of poisoning. But it also has a political constituency - all the people it employs. In that it has much in common with other "anti-industries," like the software patent mafia.