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May 29, 2009

Declaring a Truce on Cancer?

It may make more sense than you think:

Wired.com: Where do we stand now in the war on cancer?

Robert Gatenby: We’ve learned enormous amounts about the disease, but it hasn’t translated into therapy. My proposal isn’t necessarily right, but it’s an alternative way of thinking.

We’re coming at cancer with a paradigm in the tradition of Paul Ehrlich and magic bullets, which was successful in treating bacterial infections in the mid-20th century. The conscious or unconscious analogy is that we’d like to find antibiotics in cancer. We’d like to find a cure.

Wired.com: Are the dynamics of fighting cancer so very different than fighting bacteria?

Gatenby: Bacterial cells are so fundamentally different than our normal mammalian cells. Finding something that works on bacteria, but not our own cells, is much easier than finding something that distinguishes between normal and non-normal cells.

Bacteria also tend to be exquisitely sensitive to antibiotics. They develop resistance, but that occurs over a long period of time. The sensitivity of tumor cells to therapy is nowhere near as great, and they’re much more heterogeneous. You have resistant phenotypes present before you even start treatment.

Wired.com: In your article, you say that drug-resistant cancer cells are actually less reproductively fit than non-resistant cells. Why doesn’t killing off the non-resistant cells leave behind a weaker population?

Gatenby: Being drug-resistant costs cells energy. Even when you’re not giving a drug, cells are still using energy to maintain their resistance mechanisms. So drug-resistant cells don’t have that energy available for proliferation. They’re not as fit as the drug-sensitive cells, and are only present in small numbers.

That balance completely changes when you give high-dose therapy. What you’ve done then is kill their drug-sensitive competitors, and left the field open to drug-resistant cells.

Wired.com: What’s the alternative?

Gatenby: How people treat invasive species can provide an analogy for thinking about cancer therapy. In treating a field for a pest, for example, you might treat three-quarters of it with a pesticide, and leave the other quarter untreated. Pesticide-sensitive pests remain there, and they spread out into the field after treatment, preventing pesticide resistance from becoming dominant.

Using pesticides on an entire field is like what we’re doing with cancer now. And we all agree that we’d rather get rid of the pests altogether, but if you can’t do it, if every time you have an infestation you treat it and get resistance, then you try a different strategy. The alternative is to try to reduce the pest population so that it doesn’t damage your crop, and accept the fact that they’re going to be there. That’s what I’m talking about with cancer.

Wired.com: What type of treatment would that involve?

Gatenby: Instead of fixing the dose of the drugs, you fix the size of the tumor. Your whole goal is to keep the tumor stable. You continuously alter the drug, the dose, the timing of the dose, with that goal in mind.

Wired.com: Outside of your mathematical models, is there evidence to suggest that this might work?

Gatenby: With a mouse ovarian cancer model, if you treat it with a very high dose, the tumor goes away. It looks like you’ve cured it. But a couple weeks later it comes back and starts killing animals. This is a standard outcome.

What we did is use smaller doses of drugs and applied them when necessary. We were able to keep tumors stable and mice alive indefinitely.

Wired.com: So we don’t need new drugs, just different ways of applying them?

Gatenby: Of course we need to keep looking for new drugs and more effective therapies. But the lesson we can learn is that the judicious use of drugs can be more effective than the intuitive approach of killing as much as you can.

Posted by Cassandra at May 29, 2009 08:06 AM

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Two Words: Vitamin B-17.
A book: World Without Cancer

Posted by: Cricket at May 29, 2009 11:04 AM

If I understand correctly, what he's describing in terms of keeping tumors' size in check is what Herceptin does for HER2-positive breast cancer. It's not a cure but a maintenance drug.

Posted by: Elise at May 30, 2009 09:37 AM

In most cancer protocols, maintaining the size of the tumor means it is contained; it won't spread.
However, the reasoning behind alternative therapy is that if the tumor can be reduced, the cancer can go into remission.

Back in the day, chemotherapy (I am talking about 30 years ago) was not what is called 'biologically selective.' It killed all the healthy stuff too.

Posted by: Cricket at May 31, 2009 10:17 AM

Actually, Cricket, it still does kill healthy stuff, too. It's just that today's chemo is *targeting* all of the 'faster-growing-than-the-rest' cells in the body. Which is why chemo patients lose their hair as well as their finger and toe nails and can go through bouts of not being able to taste. Those cells are normally the fastest growing cells in the human body.

The stasis maintenance drugs are designed to keep cancer cells "asleep". However, this only works after they reduce the number of cancer cells to a *manageable* level. The drugs will only work when they only have to keep a certain number of cells asleep. And that has more to do with the side effects of stronger doses, than limitations of the medication. If the tumor or cancerous area is too large, then the inhibitors won't function properly -- if at all.

Posted by: DL Sly at June 1, 2009 12:15 PM

The analogy with pest management is flawed. It is not a recommended practice to keep parts of crop fields untreated. However, rotating chemical groups and use of non-chemical methods are important aspects of IPM and IRM.

Posted by: Satyabroto Banerji at June 16, 2009 11:21 AM