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Unlocking Cancer Genes

December 13, 2005 at 12:00 AM EDT
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JEFFREY BROWN: The goal is ambitious: a $100 million effort to decipher the specific genetic mutations at the heart of each different type of cancer. The first phase of the project, called the “Cancer Genome Atlas”, was announced today, and is expected to last three years.

To tell us more about it, I’m joined by scientists representing the two government organizations leading the effort. Dr. Francis Collins is director of the National Human Genome Research Institute. Dr. Anna Barker is deputy director of the National Cancer Institute.

Welcome to both of you.

DR. FRANCIS COLLINS: Thank you.

JEFFREY BROWN: Starting with you, Dr. Collins, first remind us about the connection between genes and cancer.

DR. FRANCIS COLLINS: We have learned over the course of the last two or three decades that cancer is a disease of DNA, of the genome, all of the DNA, that mutations in genes cause cells to grow out of control and force them to keep going when they really should stop, so the dominant paradigm and the pathway towards better diagnosis and treatment and even cure is to understand those specific glitches in specific genes in order to interrupt that process.

JEFFREY BROWN: And, Dr. Barker, sometimes we talk about cancer as though it’s one thing but it’s clearly not. And, genetically speaking, is each cancer a completely different thing?

DR. ANNA BARKER: We know that there are probably as many as 200 different kinds of cancer. And within each cancer — take breast cancer as an example — there are sub types. And we are beginning to understand, as Dr. Collins has just said that that is really driven by changes in the genetics. So we really are interested in pursuing these cancers along the line that Dr. Collins has just talked about.

JEFFREY BROWN: All right. So there has been a lot of research ongoing in this area in the last few years. And we’ve reported some of these — some of the research on cancer and genes, but what specifically, Dr. Collins, is new about this initiative?

DR. FRANCIS COLLINS: Well, you’re right. There have been a lot of very interesting discoveries about genes involved in cancer. We know about 300 genes that play a role in one cancer or another. And those have led us to very exciting revelations about new ways to diagnose and treat the disease.

But nobody working in this field would try to tell you that that’s the complete list. You know the story of the fellow who came out of the bar and was trying to find his car keys that he had lost somewhere on the street and so his friends came out and found him looking under the lamp post and asked why aren’t you looking elsewhere? You haven’t found them here. And he replied, well, this is where the light is.

In many ways that’s what we’ve had to do in terms of our study of genes involved in cancer. We’ve looked under the lamp post in the places that our technology allowed to us discover them. But you know what? We have got the Genome Project now. We understand the entire DNA sequence of our own instruction book.

We can light up the whole street and the goal of this project we’re launching today is to take that kind of technology, that kind of comprehensive attitude and instead of looking here and there but not everywhere, we’re going to look everywhere in a set of carefully chosen cancers and we’re going to get the complete list of what has gone wrong in those tumors.

And that’s going to lead us to a much more comprehensive and rational way to approach the disease.

JEFFREY BROWN: And you just said this carefully — a list of carefully chosen cancers. I’m going to ask you about that, Dr. Barker, because you’re starting with just a small number, right?

DR. ANNA BARKER: Right. And the characteristics of the tumors that we’re going to choose are really going to be pretty stringent.

Cancer is extremely complex. This is a feasibility study actually for the larger project.

JEFFREY BROWN: This is a pilot project.

DR. ANNA BARKER: It’s a pilot. So we really want to pick cancers that are as simple as possible, as homogeneous as possible. We want cancers that have few sub types. We want cancers that actually will produce enough material that we can actually do this project. So we have to have fairly good- sized samples for the project.

And we would like these patients that are going to give us the samples to actually be on a clinical trial. In other words, they’re being treated for their cancer and they’re being treated in similar ways, so that we get as much uniformity in the samples as possible.

We want to simplify this pilot project so we get as much information about the cancers that are chosen as possible.

JEFFREY BROWN: So who gets the money and what exactly do they do with it?

DR. ANNA BARKER: The people who get the money will be our scientific community — the basic and clinical researchers who are working in cancer biology today and in genomics research today– and we will distribute these funds as we always do through a peer-review process.

Scientists will be rigorously reviewed basically by other scientists so we pick the best people to do the project in cancer biology and genomics.

JEFFREY BROWN: And, Dr. Collins, given that it’s a pilot project, what’s the marker — speaking of markers here — what’s the marker for success? How do you know when you’ve got to a sufficient point that you can say we’re starting a larger project?

DR. FRANCIS COLLINS: We are by putting together this network that involves sample collection and technology development and applications of those technologies, are convening a very incredibly smart and capable group of researchers, but we are going to hold them to certain milestones.

And that will be part of our determination of whether this is working. So how many tumors have been examined? What technologies have been applied? What genes have we discovered that we didn’t know about before that clearly are playing a role in cancer, and which of those now give you new ideas about drug targets that you wouldn’t have thought of before?

And which of them allow you to take a tumor that you normally would have just lumped together into one category and realize, oh, that’s really three different types of cancer and they each have a different prognosis and a different potential response to therapy? Those are the things we’re looking for in this three-year period in order to decide about scale-up.

JEFFREY BROWN: As you both referred to, we have seen some cancers respond to individual treatments over the last few years. Is that the model here, to figure out the specific treatment or drug therapy for a cancer through the genome process?

DR. ANNA BARKER: Yes, that’s exactly the idea. We basically believe that this fruitful concept we’ve seen through the treatment of diseases like chronic myologic leukemia with Gleevec and Herceptin and breast cancer, these are very targeted treatments to a specific genetic defect in the cell which is really encouraging to us.

And that’s only a few of the street lamps that Dr. Collins is talking about that we’ve looked under. So we believe that this is the wave of the future in terms of specific genetic defects, specific drugs targeted to those defects, and basically not one-size-fits-all for therapy.

I mean, you have to understand that we’re actually — we have a lot of waste in the system now. If only 20 percent of the patients are responding, let’s say, to a therapy, 80 percent of the patients are not responding. If 100 percent are responding, then, you know, that’s actually exactly where we want to go with this project.

JEFFREY BROWN: Now you both know that when you announce a big endeavor like this, people want to know what it means to them.

DR. FRANCIS COLLINS: Sure.

JEFFREY BROWN: They want to understand about a timeline. They want to understand about specific therapies and drugs that might reach them because, of course, as you and I were talking about this before, Dr. Barker, you’ve had your own family experience; I think everybody in our audience has had some kind of experience. What do you tell them? How does this initiative translate to the personal level?

DR. FRANCIS COLLINS: Well, the good news is that this approach to cancer is going on today and has been going on for some years, this ability to discover genes involved in cancer and then translate that into this pipeline that leads to treatments. What we want to do is to open that pipeline wide open.

So you’re going to see and have already seen the examples that Dr. Barker just mentioned, circumstances where this has paid off and people who previously had nothing really to offer them now are being treated very effectively with some of these new targeted, rational gene-based approaches to therapy.

We will see in the course of this pilot project particularly for the tumors that are studied in advance of a significant sort in identifying more entities to put into that pipeline. But frankly we have to be realistic.

This is a tough problem. We would have figured out cancer by now if it wasn’t a tough problem. And we are now I think bringing to bear all of the high technology, high tools that the genome project has made possible.

It would not have been possible a couple of years ago. But it will take some time — this pilot project will tell us a lot. If it looks good, we’ll want to scale it up. I think you can look for a time in a decade or more where really the treatment of cancer is completely different than what we have today and the treatments we have are both more effective and less toxic.

JEFFREY BROWN: Okay. We just have time for a very short answer. Do you want to comment on that?

DR. ANNA BARKER: I think actually the output from this project may very well inform clinicians today and it may very well impact treatment much earlier than we think.

JEFFREY BROWN: All right. Dr. Anna Barker, Dr. Francis Collins, thank you both very much.

DR. ANNA BARKER: Thank you very much.

DR. FRANCIS COLLINS: Thank you, Jeff.