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Our News - In Their Own Words - Linehan Interview

The Genetic Basis of Kidney Cancer

NOTE:  This interview is an excerpt from NIH Radio Podcast, Episode 13.

Bill Schmalfeldt:
When the general public thinks about cancer, folks like me, a layman, you know, we focus on the disease itself, how not to get it, what to do if we do get it.  But then researchers at the National Cancer Institute look at the disease in other ways, for instance, kidney cancer.  What's the genetic basis for kidney cancer?  Do people inherit susceptibility to this kind of cancer?  At the forefront of this kind of research is my guest Dr. Marston Linehan, Chief of the Urologic Oncology Branch at the NCI, here at the National Institutes of Health.  Is it true that people are genetically more susceptible to kidney cancer than others?

Marston Linehan:
Well, most cancers have both an inherited or hereditary form as well as a sporadic or noninherited form of the cancer.  And kidney cancer, like prostate cancer, breast cancer has both an inherited as well as a noninherited form.

Bill Schmalfeldt:
So part of your job here at the NCI is to search for that genetic link to kidney cancer.  What can you tell us about the research you and your colleagues have done here?

Marston Linehan:
Well, we started out nearly 25 years ago now to identify the gene; we now note “genes,” for kidney cancer.  Our hope at the time was that if we could identify and understand the genes that cause kidney cancer, that might lead us, other scientists, to develop therapies to treat this disease.

Bill Schmalfeldt:
What do we know about the gene mutations?

Marston Linehan:
We started off in the early 1980s to identify the gene for kidney cancer and it took us nearly 10 years to find the first kidney cancer gene, called the VHL gene.

Bill Schmalfeldt:
There's a certain amount of having to go from hospital to hospital, I understand.

Marston Linehan:
Well, we studied families with kidney cancer and we're able to use the power of genetics to identify the VHL kidney cancer gene.

Bill Schmalfeldt:
What does VHL stand for?

Marston Linehan:
VHL stands for Von Hippel-Lindau.  That's a hereditary cancer syndrome in which patients are at risk to develop a number of cancers, including kidney cancer.

Bill Schmalfeldt:
Now that we have found this mutation, what can we do about it?

Marston Linehan:
To begin with, in the families we can now tell the family members who carries this gene, who's likely to develop kidney cancer in these families.  We can tell children who are just born, which children in the family are at risk to develop kidney cancer and which aren't.  So we're very encouraged about that.  But for us, the longer-range goal is to understand how this gene works, how it causes cancer in order to develop therapies for patients with kidney cancer.

Bill Schmalfeldt:
Are we close to developing vaccines or other treatments based on this discovery?

Marston Linehan:
Well, there's a lot of work looking at vaccines and immunologic therapy for kidney cancer and there's been great progress in that area.  Our focus is understanding the cancer gene and its pathway and this work has led us, as well as other scientists, to understand this pathway.  And the FDA approved two drugs in the past year that target this pathway in patients with kidney cancer.  So we're very encouraged about that.

Bill Schmalfeldt:
So by FDA approval, these drugs are available now?

Marston Linehan:
Yes, they are.

Bill Schmalfeldt:
Well, discoveries like this tend to have a ripple effect, where you find an application for a specific disease and then find that this also has applications in other areas.  Is that the case with this research?

Marston Linehan:
Yes.  In other words, finding the gene for the inherited form of kidney cancer; it turned out this gene was also the gene for the noninherited or sporadic, the common type of kidney cancer.  So studying these families, these wonderful brave people who were and are our partners in this work, and who came here to the clinical center, NIH, to be studied, this work has benefited those patients but it also benefited so many other patients who have noninherited kidney cancer.

Bill Schmalfeldt:
It seems like for every time we answer a question, five more pop up, if not more.  What are some of the more important unanswered questions that are still out there in this field?

Marston Linehan:
When we started this work nearly 25 years ago, kidney cancer was thought to be a single disease.  We now know that kidney cancer is not kidney cancer.  It's not a single disease.  It's a number of types of cancer that just happen to occur in the kidney.  They have different histologic types, different types of kidney cancer.  They react differently in patients.  They have different clinical courses.  They respond differently to therapy and they're caused by different genes.

So, in other words, kidney cancer we use to think of as a single disease, we now know it's five or six diseases, at least.  And some types of kidney cancer have as much in common with each other as breast cancer does with colon cancer.  Our understanding of the genes that cause kidney cancer is that each different type is a different disease and that potentially they're going to need different therapies, therapies targeting those pathways.  So when we first identified the VHL kidney cancer gene, that was in 1993.  We and others have been working on that gene and its pathway now for 13 years and we've learned a lot.  But we still have a lot to learn.

We are encouraged about the progress that's been made, but we still have a long way to go.  But we're very encouraged about the fact that these new medicines that were approved by the FDA this year have had response in a number of patients.  We're very encouraged about that.  However, we need better agents, agents that target the pathway even better than those agents and combinations of drugs.  So we have many, many things to do, but we're very encouraged about the progress of the work.  The nation's biomedical investment in biomedical research is really paying off.  Our work is because we focused on one disease: kidney cancer.

However, we work with colleagues from very different fields, from colleagues from the Genome Institute, colleagues who had genetics background who we learned a lot from.  Colleagues from medical oncology and all sorts of different backgrounds that enabled us to do this work.  So the work that those people did, even though they weren’t working on kidney cancer directly has really benefited our work and we think our work has helped them.

Bill Schmalfeldt:
I always like to end an interview with this question.  Is there anything you like to add?

Marston Linehan:
I think it's just that we are very encouraged about the progress of the work, understanding cancer genes and developing therapies to target those pathways.  I'm very optimistic about the future and hopeful that this type work will lead to effective forms of therapy for every patient with kidney cancer.

Bill Schmalfeldt:
Dr. Marston Linehan, Chief of the Urologic Oncology Branch here at the National Cancer Institute.  Thank you so much for spending a few minutes here with us on NIH Research Radio.

Marston Linehan:
Thank you.

[end of transcript]

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