Report from the war on cancer


ONE OF the most remarkable breakthroughs in the past two decades is the discovery that cancer is a genetic disease. Human genes are being identified at such a rapid rate that this new knowledge promises a new era of prevention, treatment and cures.

Dr. Richard Klausner, director of the National Cancer Institute in Bethesda, addressed these issues during a recent press conference at a meeting commemorating the 40th anniversary celebration of Jackson Laboratory in Bar Harbor, Maine.

The laboratory is the world's preeminent center for mouse genetics, and it has played a major role in setting the pace for human gene discovery.

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Q: The goal of the Human Genome Project is to discover all of the approximately 100,000 genes that occur in every cell. Learning how these genes misbehave to cause disease promises to revolutionize medicine. How will people first encounter this revolution?

A: I really believe that a lot of the application of genomics and genetics in tailoring and targeting interventions is going to happen first in cancer. The doctors who treat cancer are conceptually ready for it. The tools are there, and the disease itself is amenable to it. This will allow us to very rapidly, over the next few years, rethink our classification of cancer and change the way we diagnose and treat it.

Q: Does going from looking at cancer cells under the microscope to examining their molecular construction represent a new era?

A: It's a turning point. It's time to make the transition from the old approach, the description of cancer, to what we know has to be the future approach, which is a systematic molecular description. That's where the real understanding of cancer lies.

Q: How has the National Cancer Institute capitalized on this movement?

A: We instituted a program called the Cancer Genome Anatomy Project because we needed to know all the genes that were actually at work in normal cells, malignant cells and everything in between.

Q: Knowing the genome sequence from beginning to end will be spectacular but will it tell you which genes are involved in cancer?

A: The genome anatomy project was the first to discover genes and turn that discovery into a really searchable encyclopedia of which genes are on or off in which cancers.

Q: Why has the progress in curing and preventing cancers gone so slowly?

A: That we have only a 30-percent successful response rate in cancer is almost undoubtedly due to the mixing of diagnoses. We know that. We haven't had the right drugs because we lump too many cancers into the same class. In testicular cancer, for instance, the same drug that cures most patients has no effect on a small fraction of them. I absolutely believe that this is not bad luck. It is because they're not the same disease, although we now call them the same.

Q: Is gene-based therapy for cancer still a long way off?

A: No. We're already doing it for breast cancer. We're not treating anyone with Herceptin who doesn't [produce excessive amounts of] the HER2neu gene protein, and we don't treat women with tamoxifen who don't show the gene for the estrogen receptor.

Q: How will the NCI use the new devices called chips, which are about the size of a credit card and contain DNA sequences to find out what kind of genes a person has? Can they be used to improve cancer diagnoses?

A: We have a whole variety of trials that are using them for molecular classification. We actually just opened the first clinical trial at the NCI that is using these chips to literally follow every day the gene patterns in chronic lymphocytic leukemia patients every time they receive drug therapy. It's really quite extraordinary. The patients are beginning to fall into different genetic categories where you can see different responses in the tumors.

Q: It's one thing to do this kind of research at a top-level facility like the NCI, but how are you going to make sure it becomes more widely available?

A: We will fund 24 cancer array centers around the country. That's a lot in terms of the rapid dissemination of this new information. That will be done over the next couple of months.

Q: After you get the molecular patterns of cancer, is it going to be difficult to figure out which patterns are meaningful?

A: We have to make correlations between patient outcomes and the clinical characteristics of cancer so that we can use individual molecules to identify individual cancers. The better molecular diagnosis is, the more it will choose those molecular characteristics that so perfectly define the tumor that they will become the targets for therapy and prevention.

Q: Will this line of research lead to better therapies that are fundamentally different therapies for cancer?

A: When you have a treatment or prevention, it should be tailored for a specific disease. You don't treat viral diseases with antibiotics, for instance. The second aspect is targeting. We not only want to use the molecular characteristics for correct diagnostic classification, so we can tailor therapy, but then we also want to know the details of that molecular machinery so that we can design therapy that is targeted to the machinery of that cancer.

Q: Thousands of scientists are involved in research on the molecular classification of cancer. How will you bring their research together to make sense of it?

A: We'll soon invite all the investigators to Bethesda for the first time. We will sit down and say how are we going to create a shared language for this enormous amount of information, because it doesn't exist anywhere. Our goal, over the next year or so, is to develop a language and database that everyone agrees on, that will allow everyone to share the data from these studies.

Q: Will this common language lead to therapeutic breakthroughs?

A: Yes. We're beginning to see that many different cancers share the same genetic mutation. For instance, a particular gene mutation may occur in 30 percent of brain cancers, 40 percent of breast cancers, 60 percent of prostate cancers and 15 percent of gastric cancers. That would be important to know if we have a great drug for treating cancers that have that particular genetic alteration.

Q: As these new advances come about, how can you make sure that patients get them?

A: One of the big problems is the disparity between the advances and the adoption of those advances in cancer care. This disparity occurs because of many reasons. We need to develop a surveillance system to identify what is cancer practice. We don't have any way of knowing how doctors actually practice oncology. It's one of the things we're struggling to solve now.

Ronald Kotulak is a Chicago Tribune science writer.

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