Archives for June 2016

Pancreatic cancer really pisses me off.

I’ve known too many good people struck down too early by it, and in two generations we haven’t really improved cure rates significantly. Besides being highly resistant to most forms of chemotherapy, pancreatic cancer is almost never diagnosed at an early stage. By the time patients develop the typical belly pain radiating to their backs, jaundice, or loss of appetite, it’s already too late. We’ve yet to find a reliable blood test or routine scan that’ll help, and that pisses me off even more. And though most every pancreas cancer patient can, in retrospect, identify vague symptoms that started months beforehand, they aren’t enough for people to seek care – or much for a doctor to go on if they do. We’re badly in need of an innovative idea.

But whaddya know, Microsoft has one –and it’s way out of left field.

Turns out, most people with undiagnosed pancreatic cancer have recurring patterns of internet searches in the months preceding diagnosis. A team of Microsoft analysts parsed the internet search histories of 9.2 million people over 18 months, and identified query clusters – things like “itching”, “oily stool”, “taste changes” – that could predict who had undiagnosed pancreatic cancer and who didn’t.

(Ignore that popping noise, it’s just my mind blowing out of my ears.)

The potential applications of this concept go far beyond pancreatic cancer. Besides screening, this approach could refine our understanding of symptom patterns in almost any disease.

The approach is a long way from workable, and there are some very thorny privacy concerns:  most people have a healthy skepticism of “big data”, and the intentions of those who mine it.

But the concept surprises and excites me.

The full report is here and reported in the New York Times here.

As fruitful as genetic research has been in oncology – and will continue to be – it might be that we’re playing to our enemy’s strengths.

Sun Tzu would shudder.

For starters, the genetic code of even a single cancer cell is unfathomably complex. Second, not all cancer cells in an individual patient are identical – genetic drift gives rise to subpopulations that behave very differently. Every oncologist has seen mixed responses to treatment: some of a patient’s tumors shrink while others get bigger. There’s a lot of variability even in the same types of cancer. Not all cases of breast cancer, for instance, have the same mutations. And in different cancer types the differences are even more daunting.

It’s an infinity of variation, with few common themes. And highly targeted drugs have so far all had the same shortcoming – each one helps only a small minority of patients. It’s like the difference in utility between a screwdriver and one particular socket wrench attachment – the more specific the tool, the more different types of tools you need.

But some researchers are looking for the Phillips screw that most cancers have in common. And they think the metabolic processes of cancer cells might be it.

Like all living cells, cancer cells require fuel to survive and thrive. And across all cell types in every form of life we know, nature’s come up with very few workable solutions. A relatively few types of molecules can serve as fuel. And there’s a finite number of ways to transform that fuel into energy. Think of automobiles, for instance: though there’ve been countless modifications to the basic engine, it still operates on the principle of internal combustion.

Mammalian cells process fuel in two dominant ways: aerobic metabolism (requiring oxygen) and anaerobic metabolism.

We’ve known for years that cancer’s glucose metabolism is deranged – popularly over-simplified as “cancer loves sugar”. It tends to favor the highly inefficient anaerobic metabolism. It’s terribly wasteful, and turns caner cells into “sugar hogs” – likely to the detriment of the rest of the organism.

But the insight hasn’t yet given us new treatment tactics. See blog: Does sugar cause cancer cells to grow? click here

And no, you can’t simply starve the cancer by avoiding dietary sugars. Sorry folks, that’s just a myth.

But the metabolic differences across cancer types may be very few. And that might just give us a focused area to attack.

Read more about it here: NY Times – An Old Idea, Revived: Starve Cancer to Death

I once read that the amount of raw medical knowledge doubles every decade. I can’t verify that, but it sure seems right.

Not every new fact brings a new solution. Most new drugs and clinical trials are, in fact, blind alleys. But to paraphrase Edison, it’s no failure to identify with certainty the 10,000 things that absolutely positively won’t work. Because one day, if you keep at it, one glorious day you’ll find something that will.

I’ve never been a dewy-eyed optimist about cancer medicine, preferring instead unflinching honesty and a quiet faith that things would get better. Lately, I’ve had to check my curmudgeon hat at the door – because in the last few years, the rate of progress has been bloody astounding.

Think about this: in the middle of the last century, there were less than six drugs approved for use in cancer. Now there are over 170…and the majority appeared in the last decade.

Three new drugs for myeloma? In a few months? Are you kidding me? PD-1 inhibitors rewriting the natural history of metastatic melanoma (ask President Carter) – and they work in lung cancer too?

Pinch me. I can’t possibly be awake.

And yesterday, Vice President Joe Biden launched the National Cancer Institute’s Genomic Data Commons. It’s a public repository and analytic resource allowing every map of every cancer gene known to be brought together in one place.

Up until now, it’s as if different groups have been working on separate sections of a very large jigsaw puzzle – some doing the left corner, some doing that blob of blue sky, some doing whatever that tan thing is, all making incremental progress on separate small areas. But if you’ve ever done a jigsaw puzzle, you know how fast you finish when you start putting the sections together.

Just think about that – open source hacking, by every cancer researcher in the world.

This is actually happening, folks.