What if we didn’t try to cure cancer, but simply kept tumors from growing too big? That’s what radiologist Robert Gatenby of the Moffitt Cancer Center proposes this week in the journal Nature.
Gatenby argues that high doses of powerful chemotherapies wreak havoc on a patient’s immune system and foster the rapid regrowth of chemoresistant cancers that doctors have no hope of fighting. So instead of curing cancer, he suggests doctors aim to stabilize the tumor at a tolerable size.
In practice, this would mean that doctors identify a target size for an individual tumor that gives the patient the best quality of life. Then, they will regularly monitor the tumor’s growth with medical imaging equipment like a PET/CT scanner (see photo), and regulate doses of anticancer drugs to maintain it at a precise volume.
To find out more about what is bound to be a controversial proposal, we spoke with Gatenby, 57, who recently founded a new program in Integrative Mathematical Oncology at the cancer center.
[An edited transcript of the interview follows]
How do we fight cancers today?
The paradigm we typically use to fight cancers right now comes from trying to treat bacterial infections. We are always looking for the “antibiotic” to kill the cancer cell. The most common strategy is high dose density therapy: give the highest possible does in the shortest period of time. This is the classic therapy that makes everybody sick.
Why doesn’t that work on many cancers?
By giving a high dose therapy, you eliminate all of the sensitive population of cells and allow resistant cells to grow up at the maximum rate. You get the evolution of resistant cell types under these high dose therapies. The mathematical models we’ve looked at suggest that there will always be populations of cells resistant to therapy present in the tumor.
In your article you suggest that we treat cancers like invasive species. What do you mean by that?
We have the wrong analogy when it comes to treating cancer. Instead of the analogy between cancer and bacterial infections, we should be using an analogy between cancer and invasive species. The goal is not to eliminate pests because applied ecologists have learned that’s futile. Instead what they’ve learned to do is to keep the pests at a tolerable level. This is called “integrated pest management,” and it became a policy of the agricultural department when Richard Nixon was president.
What we’ve discovered from our mathematical models is that the best management strategy for a non-curable cancer is not one where you kill the maximum number of cells possible but when you kill the minimum necessary. You don’t want to eliminate all the chemosensitive cells because they can suppress growth of the tumor.
What evidence do you have that this approach could work?
We’ve done some experimental work on ovarian cancer in mice that’s going to be published next week in the journal Cancer Research. If you treat this cancer with high doses of carboplatin (platinum based chemotherapy) the tumor will melt away and apparently disappear. But within a few weeks it will come back, regrow, and kill the animal.
What we did instead of the traditional therapy of giving fixed amount of drug at fixed intervals, we fixed the tumor size and give only enough drug to keep the tumor stable. With progressively smaller doses of therapy, we were able to keep the animal alive indefinitely without symptoms. It is very preliminary evidence.
What sort of criticism have you received of this strategy?
About two months ago, I submitted a grant and the response was a mixture of horror and contempt. The crux of the response was that patients and physicians would never accept the idea of not treating for cure. The psychology will inevitably be a significant problem for the acceptance of a therapy that explicitly does not aim for a cure.
To give you an example of the kind of shift that needs to occur, a favorable response to a therapy today is considered a reduction in tumor size, but I argue that that may not be a favorable outcome because you’ve eliminated sensitive tumor cells. If you try to treat for cure with hundreds of patients, and you haven’t cured anybody then at some point you have to make the decision that treatment for cure is futile. It just makes common sense.
Image of a PET/CT scanner via Flickr from joncallas