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Cancer researcher Marston Linehan discusses role of genetics

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Marston Linehan, chief of urologic oncology at the National Cancer Institute, bridges the gap between genetics research and treatments for cancer. He might analyze a heritable form of kidney cancer in the lab one morning and later that day remove that same cancer from a patient in the operating room a few hundred steps away. Linehan and his colleagues have identified four particular genes for kidney cancer; as a result, several viable drug treatments are now available. Linehan’s surgical techniques have also improved thanks to a better understanding of genetically distinct kidney cancers. We joined Linehan on the short walk from the operating room to his office to talk about genetics research and its effect on the war on cancer.

— Christian Torres

How does a urologic surgeon go from surgery to genetics?

When I came [to the National Cancer Institute] in 1982, we were seeing a lot of patients with kidney cancer, and the majority of those patients were dying. About 300 drugs had been tried in patients with kidney cancer, and none of them worked.

With my colleague Bert Zbar, I decided to try and find a gene for kidney cancer. My thinking was: If we could identify the gene for kidney cancer, that might provide the foundation for the development of a therapy for this one cancer. We had no idea what a mountain it would be to climb.

It took you 10 years to find the first of four genes that were related to kidney cancer. Was it easier to find the later ones?

The second one took us about five or six years to find, and the third was about four or five years. This was done by tracing genes in families. Now, with the Human Genome Project, we could probably do that work in six or 12 months.

The Human Genome Project was a major milestone for cancer research and other medical fields. The NIH has a new, more focused project called the Cancer Genome Atlas. What is the atlas, and how does it tie in to your work?

We’ve been looking at kidney cancer genes for 30 years, and now, to have this wonderful effort, it’s a miracle. The Cancer Genome Atlas is sequencing the genes from multiple cancer types: kidney cancer, prostate cancer, bladder cancer, breast cancer, colon cancer. I’m working on the project just with kidney cancer. We are very hopeful about this, to put it mildly.

What’s the overall goal of the atlas? Is it simply to find particular genes so that we can better tailor therapies?

We can not only better tailor therapies, but also we ought to be able to predict better which patients are at risk.

When I started working on this disease, there were 19,000 Americans [each year] who developed kidney cancer. In 2011, it’s estimated there will be over 60,000 patients with kidney cancer. It’s one of the most rapidly increasing cancers in the country. So why is that? If we can predict early, we should be able to prevent these people from dying.

How has understanding the genes for kidney cancer changed the way you handle surgery?

[In] patients whose cancer is clear-cell — caused by the VHL gene — their tumors are very slow-growing, and we will not recommend surgery until those tumors get to a certain size. . . . On the other hand, we have patients where it’s a different gene. Those cancers can be very aggressive, and they can spread when they’re very small. Those patients we operate on right away, and when we do surgery, we do a much wider operation because the cancer can spread throughout the kidney and get into the adjacent tissues very easily.

You decided to go into genetics because you were frustrated seeing patients die of kidney cancer. You’ve had success now and been able to save lives. Do you still feel that same frustration?

I do every time we lose a patient. It makes me want to say, “Let’s cancel vacations and work longer.” I grieve with the patients’ families, as do all of our staff . . . . But we’re also starting to have more and more successes, and that encourages people. Whenever we have a success, we all recognize that this is what we’re working toward.

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