SHOW: TALK OF THE NATION (2:00 PM ET) June 1, 2001, Friday

ANCHORS: IRA FLATOW

IRA FLATOW, host:

This is TALK OF THE NATION/SCIENCE FRIDAY. I'm Ira Flatow.

Every year, more than half a million Americans die of cancer. Only heart diseases kills more people in the US. And this year, 30 years after Richard Nixon declared a war on cancer, still only a small number of cancers can be cured today. But now these decades of basic cancer research are beginning to bear fruit. Researchers have learned that cancer is not one disease, but many. They know that cancer cells have genetic mutations that make them grow out of control. And they had added the words 'oncogene' and 'tumor-suppressor gene' to our vocabulary.

Up until now, the standard way to fight cancer was to surgically remove it and to use toxic drugs or radiation to kill the cancer cells. But often these techniques attack more than just the cancer, leaving people nauseous and weak. Now scientists are working on a new class of drugs that block the faulty signals in the cancerous cells. And unlike chemotherapy or radiation, these so-called drugs targeted drugs are designed to attack only tumorous cells and leave healthy cells alone. Not all of these new, targeted drugs work as well as Gleevec, which was approved by the FDA last month in record time. And it is possible that the cancer cells will grow resistant even to the targeted drugs after a while. But many doctors believe that these new drugs are a better way to attack cancer, and may turn it into a chronic disease someday instead of a disease that will kill you.

This hour, we'll talk about Gleevec and other targeted drugs, how they work, how effective they are, what side effects they have and what we can expect from them realistically in the future and what other kinds of treatments may be on the cutting edge of research. So we know you're very interested in this topic. And if you'd like to join in, give us a call. Our number is 1 (800) 989-8255; 1 (800) 989-TALK. And as always, if you want more information, you're welcome to surf over to our Web site at sciencefriday.com.

Now let me introduce my guests for this hour. First up is Dr. Vincent DeVita, who is professor of medicine and director of the Yale Cancer Center. And from 1980 to 1988, he was the director of the National Cancer Institute, and he joins us from Yale.

Welcome to the program, Dr. DeVita.

Dr. VINCENT DeVITA (Director, Yale Cancer Center): Good afternoon. Nice to be here.

FLATOW: Thank you.

Dr. Brian Druker is a professor of medicine and the director of the Oregon Health and Science University Leukemia Center in Portland, Oregon, and he joins us today by phone.

Welcome to the program, Dr. Druker.

Dr. BRIAN DRUKER (Director, Oregon Health and Science University Leukemia Center): Thanks for having me, Ira.

FLATOW: You're welcome.

Dr. Jerome Groopman is the chief of experimental medicine at Beth Israel Deaconess Medical Center, and professor of medicine at Harvard Med School. And he is author of an article in this week's issue of The New Yorker magazine. The article's entitled The 30-Years War: Have We Been Fighting Cancer the Wrong Way? He's on the line from his office in Boston.

Welcome to the program, Dr. Groopman.

Dr. JEROME GROOPMAN (Chief of Experimental Medicine, Beth Israel Deaconess Medical Center): Thank you for having me.

FLATOW: You're welcome.

Dr. Dennis Slamon is director of the Revlon/UCLA Women's Cancer Research Program at the Jonsson Cancer Center at the University of California at--UCLA. And he's joins us from Los Angeles.

Welcome to the program, Dr. Slamon.

"Our concern is that resistance could develop over time. And as long as we can detect even traces of the leukemia, we'd much rather have people on what seems to be a relatively non-toxic therapy than deal with a relapse of leukemia."

Dr. DENNIS SLAMON (Director, Revlon/UCLA Women's Cancer Research Program): Thank you.

FLATOW: Dr. DeVita, let's begin with you. We've heard a lot about targeted cancer therapies recently. Give us an idea. What are targeted drugs, and how do they work differently from regular cancer therapies?

Dr. DeVITA: If I may, Ira, though, I'd like to start out by giving us a foundation that reflects a little differently than the way you introduced the subject about few people being cured. You know--because over half of patients in this country with cancer are curable, and are cured each year. The mortality rate...

FLATOW: Half the patients are cured?

Dr. DeVITA: Over half of all patients with cancer today are cured, period.

FLATOW: I stand corrected.

Dr. DeVITA: And mortality rates are dropping, incidence rates are dropping. So I think we shouldn't be too pessimistic.

However, most of that was done with therapies that were designed to kill cells that are going through metabolic processes, dividing and so forth. And they do damage bystander cells. The targeted therapies--or the type the Dr. Druker will tell you more about--aim at a specific lesion that's unique to the cancer cell, or at least predominantly found in the cancer cell. In the case of Gleevec, it's unique. And so that they can kill cancer cells without causing damage to bystander cells. And optimally, that's the preferred way to go. You can get the therapeutic effect and you get no side effects, and it puts cancer in the place where I think it becomes one of the most preventable and treatable chronic diseases that we face today.

FLATOW: Mm-hmm. Let's talk about...

Dr. GROOPMAN: You know...

FLATOW: Go ahead.

Dr. GROOPMAN: Hi, this is Jerry Groopman.

FLATOW: Yes.

Dr. GROOPMAN: Vince, I'm just curious. I mean, the--my understanding is--when you say that half of all cancers, you're not talking about basil cell or sort of trivial cancers. You're talking about the major cancers.

Dr. DeVITA: No. We exclude 400,000 skin cancers, which are 90 percent curable.

Dr. GROOPMAN: Right. And the--in terms of early detection, isn't most of that related to detecting breast cancer through mammography or colonoscopy and interventions like that?

Dr. DeVITA: Not at all. Not at all. Absolutely not.

Dr. GROOPMAN: Mm-hmm.

Dr. DeVITA: You know, 60 percent of colon cancer patients are curable by surgery. But the earlier you get it, obviously, the best--the better it is.

Dr. GROOPMAN: No--but that hasn't changed in 30 years, has it?

Dr. DeVITA: I'm sorry. It's been dropping--mortality from colorectal cancer's been dropping for 20 years steadily. And for breast cancer, it's been dropping recently. So I think there's a misperception.

Dr. GROOPMAN: Because of early detection, don't you think?

Dr. DeVITA: Because of early detection and treatment. In colon cancer, it's 50-50. In breast cancer, it's a little bit more early detection. But I don't know why there's a distinction between early detection and treatment.

Dr. GROOPMAN: No, no...

Dr. DeVITA: The issue is you don't die of cancer uniformly. I don't want to create the wrong impression with the listening public that they get cancer and it's a death sentence.

FLATOW: Well, now you're creating the opposite, that everybody's living from cancer.

Dr. DeVITA: Well, I tell you every--55 percent of all patients who are diagnosed with serious cancers today are cured. But that leaves a lot of people--as you said, 500,000 people who are dying. And it leaves the people who are cured sometimes forced to use therapies that are difficult. But I don't think we should just erase everything and go to ground zero and say that people get cancer, they die of it. It's not true.

FLATOW: Well, I don't think anybody's saying that.

Let's talk about Gleevec, Brian Druker. Which--Gleevec is what, and how does it work? Tell us why that's different and why it's working.

Dr. DRUKER: What's different is--has to do with some of the things you've already talked about, and that's decades of research paying off. With this particular type of leukemia called chronic myeloid leukemia, we understood exactly what caused the uncontrolled growth of the white blood cells. A drug was targeted to shut down that abnormality and specifically that abnormality. And that's exactly what we saw in our clinical trials.

FLATOW: Do you...

Dr. DRUKER: Patients' blood counts rapidly returned to normal, and side effects have been minimal. It's exactly what you want with a targeted drug therapy. It attacks the specific abnormality that's unique to the cancer.

FLATOW: And give us an idea of the mechanics of how that works.

Dr. DRUKER: The uncontrolled growth of this leukemia is caused by an enzymatic activity that normally should regulate cell growth.

FLATOW: Mm-hmm.

Dr. DRUKER: And it's almost like the light switch or the accelerator got stuck on. There's an abnormality created in this leukemia that alters this enzyme and it's just stuck on, signaling the white cells to grow continuously. This drug Gleevec was designed by scientists at Novartis and tested in my lab, and we showed that it completely shuts down this enzymatic activity that's triggering the white cells to grow.

FLATOW: Mm-hmm. So then it's not killing the cells. It's just shutting their spread down.

Dr. DRUKER: Well, what's interesting about most growth signals is they also send survival signals. They help the cell survive. They give it not only a growth advantage, but also a survival advantage over its neighbors. And when you shut down that signal, you shut down both the growth and survival signal. And you also restore the normal cells with a bit of an advantage over the cancer cells in this case. So actually, they do die.

FLATOW: So this is a cure then.

Dr. DRUKER: Well, we're not prepared to go there yet. We have people that are doing incredibly well on therapy and--for up to two years. A few of our patients--maybe 5 percent or 10 percent--we can't detect traces of their leukemia. But we still have a lot more to learn. We still need to know about the long-term duration of these responses.

FLATOW: So they have to take--let's say it does work as it goes on, and it works for many, many years. Does that mean that you have to take the drugs for the rest of your life?

Dr. DRUKER: Right now, we're recommending people stay on this medication. Our concern is that resistance could develop over time. And as long as we can detect even traces of the leukemia, we'd much rather have people on what seems to be a relatively non-toxic therapy than deal with a relapse of leukemia.

FLATOW: Mm-hmm. And how effective might the Gleevec be on other kinds of cancers?

Dr. DRUKER: Well, we know that it's effective on a particular form of intestinal cancer. It's a relatively rare form called gastrointestinal stromal tumor. It's my view--and I'm somewhat skeptical that it's going to be that widely applicable to other cancers because it's not clear to me that they're driven by the abnormalities that are targeted by Gleevec.

FLATOW: Mm-hmm.

Dr. DRUKER: Each--as you mentioned in your opening, cancer is many different diseases. There are many different abnormalities that drive the growth of each and every cancer. We've got to figure out what those abnormalities are first.

FLATOW: Now it's been the case in many supposed therapies for cancer and other diseases that it works for a while and then--these cancers and these diseases, they're pretty tricky. They find ways of becoming resistant to the drugs themselves. Are you seeing that with Gleevec at all?

Dr. DRUKER: In a few percent of our patients, we have seen that. And I certainly share that concern, that over time we could see a resistance in our patients. We're already beginning laboratory work to look at how resistance could occur, why it does occur, if it is occurring and mechanisms to circumvent that resistance. And we're already beginning other studies combining Gleevec with other agents to try and prevent that from happening in the first place.

FLATOW: Mm-hmm. Dennis Slamon, you helped develop Herceptin, a drug that is already in use for treatment of breast cancer. Does that work, basically, the same way that Gleevec does, or is it just similar?

Dr. SLAMON: It is not directed against the same target. It's directed against a different target, which happens to be the HER2 receptor.

FLATOW: But it's a directed kind of...

Dr. SLAMON: Exactly.

FLATOW: ...affecting only the cancerous cells.

Dr. SLAMON: Right, only the cancerous cells that have the alteration.

FLATOW: Mm-hmm.

Dr. SLAMON: In about 25 percent to 30 percent of women who develop breast cancer, this alteration exists. It's not something that's inherited. It's acquired sometime during the course of the life of the individual. Why they get it we don't know. That's an area of active research.

But when it does happen, it appears to be a driving feature of the cancer. That means--just like Brian has explained to you--if you can identify one of the driving features you can attack that and, presumably, theoretically, develop something that is more effective and less toxic. The Herceptin trials have shown us that when we do target this molecule effectively, we can have some fairly profound effect on patients with disease that are driven by this.

FLATOW: Mm-hmm.

Dr. SLAMON: It is not for all of breast cancer, but about--as I said--25 percent to 30 percent. And with 180,000 new cases a year, that represents a fairly large number of patients who have the alteration.

FLATOW: Mm-hmm.

Dr. SLAMON: This receptor, like all of our targeted therapies, is going to hit some molecules that are present in normal cells. There's not going to be, I don't believe, any free lunch for any of these targeted therapies. But the toxicity profiles are remarkably different than the toxicity profiles we've seen with our traditional therapies.

Gleevec has been, really, a remarkable drug to watch because we take patients with whom--or to whom we have done pretty remarkable things therapeutically in terms of having a dramatic negative impact, things like bone marrow transplant patients, where we make the patients quite ill and can, in fact, cure some of the patients. But the cost is considerable in terms of toxicity.

FLATOW: Mm-hmm.

Dr. SLAMON: Here you have a drug that's an oral drug that they take. And you can see, as Brian as mentioned, remarkable reversals of their white counts and dropping of the counts and normalizing in the counts in many of the individuals, and normalizing of the bone marrow. But once again, there's no free lunch. There is toxicities. They are minimal, however, compared to what we traditionally see.

I heard one presumed expert talking the other night about the fact there was no toxicity with Gleevec. In fact, we are one of the centers that participated with Brian on those trials, and there are. There's liver toxicity. It's infrequent, and it's reversible. There's edema, fluid retention and there's occasional GI bleeding. And there's some recent data there may be some glaucoma with long-term use of the drug. But all of that's very minimal compared to what normally happens with chemotherapy. And by comparison, it's night and day.

Dr. DeVITA: And it's about the same--this is Vince DeVita. It's about the same as aspirin, which has side effects.

Could I add a point here, too?

FLATOW: Sure. Sure.

Dr. DeVITA: Because I think Dennis would agree with me, is that it's turning out that Herceptin and other monoclonal antibodies to targets on the surface of the cell that are expressed in some normal cells are turning out to be very non-toxic to normal cells. There's a receptor called the TGF receptor which is being targeted now as a therapy with some antibodies that are expressed very, very vigorously by the liver. And yet, when you give the antibody to the people, they have no side effects.

So it looks like the normal cells are able to compensate much better than a cancer cell. A cancer cell is vulnerable by having so much activity that it's killed more readily. So even when they are not as specific as Gleevec, they tend to work much better in cancer cells than they do--harm normal cells.

FLATOW: All right. We're going to take a quick break and come right back and talk lots more about Gleevec and other targeted kinds of therapies and take your questions. So don't go away. We'll be right back after this short break.

I'm Ira Flatow, and this TALK OF THE NATION/SCIENCE FRIDAY from NPR News.

(Soundbite of music)

FLATOW: Welcome back to TALK OF THE NATION/SCIENCE FRIDAY. I am Ira Flatow. We're talking this hour about targeted cancer drugs with my guests Dr. Vincent DeVita, Dr. Brian Druker, Dr. Jerome Groopman and Dr. Dennis Slamon. Our number: 1 (800) 989-8255.

Dr. Groopman, you outlined very well in your New Yorker article the history of targeted gene therapies, and you begin talking about the work of Robert Weinberg at MIT, and the fact that this really does piggyback on decades of research. Correct?

Dr. GROOPMAN: Yes. I mean, I think this is a time, clearly, of great hope, and we're beginning to see the first fruits of basic research after decades of investigation. It really--the first discovery of the oncogene was Harold Varmus, understanding that, essentially, the seeds of cancer, if you will, are within our own genes. It's rare that they're carried into us by a virus. But it's changes in those genes that lead to cancer. And Weinberg moved that work, showed its relevance to human cancer. And then as you said, Ira, in the introduction, showed the role, as well, of these so-called tumor-suppressors, which act as breaks on the growth of the cell.

I do think, though, and I raise caution in the article because I think at the time of great hope, we also have to be careful not to overpromise, and particularly, not to set time lines. The one lesson, I think, we can learn from the war on cancer is we can't predict when breakthroughs occur and how profound and how lasting the effects of any new drugs will be. So that there's a long history of saying that cancer will be cured in five years.

And, as you said, that whole idea of cancer as a single entity is a misconception, or that we'll reduce the mortality rate by 50 percent within 10 or 15 years, or that--as some of the articles in the papers recently--that within 15 years, cancer will be a controlled disease and you'll pop a few pills. I think that doesn't really represent to the public accurately where we are. We're incredibly hopeful, incredibly positive, moving on many fronts. But I think it's impossible to say what the future will bring and when.

FLATOW: Dr. DeVita, would you agree?

Dr. DeVITA: No, I don't. I think his view is far more pessimistic. And I think there's equal danger of creating pessimism for the public. Because we've made steady progress. It isn't the fruits of basic science paying off and, 'Eureka! We now have something that they use to treat cancer.' We've been effectively treating cancer for a long time. However, the fruits of the molecular revolution are starting to pay off to give us the more specific therapies that we've always looked for. So I think--I know Jerry well and he's not intending to do this. But I think the article and his approach to it is too pessimistic.

Dr. SLAMON: I would identify...

Dr. DeVITA: The fact of the matter is if you look...

Dr. SLAMON: Excuse me. I would agree with what Vince just said. I think for anyone to make any wild promises to the public would be irresponsible. But there is little question from anybody who knows this field well that the approaches are fundamentally different than anything...

Dr. GROOPMAN: Oh, I agree, Dennis.

Dr. SLAMON: ..than anything we were doing a decade ago.

Dr. GROOPMAN: Yes. But I agree. And I said when I started my remarks, it's a time of great hope and that there are new approaches. But there are many, many statements in the media--in Barron's last week, in Time magazine. Michael Gordon, University of Arizona, concludes the Time article by saying, 'In 20 years, I may be out of a job,' meaning that cancer will be cured and that oncologists no longer will be laboring. People say in 15 years, you'll pop a few pills and it'll be like hypertension. We can't say that.

Dr. DeVITA: And they will--well, you can't, but it's possible.

Dr. GROOPMAN: Well, think about it, Vince. There are--let's say as Harold Varmus was saying the other night on the program we shared. You have 20 or 25 major cancers.

Dr. DeVITA: A hundred.

Dr. GROOPMAN: You might have two or three or five parallel pathways of growth. You have--as Bert Vogelstein at Hopkins pointed out--the lack of the tumor-suppressor p53, which is very hard--despite the McCormick work at San Francisco--to replace. That means we'd have to develop, you know, a whole series of Gleevecs which can be each individually developed, put together and cure pancreatic cancer and breast cancer of different types and lung cancer, and so on.

Dr. DeVITA: Nobody be...

Dr. GROOPMAN: I think that I am not pessimistic. I'm incredibly hopeful. But I think we have to be careful in setting time lines because in the past, we've set them and we've been wrong.

Dr. DeVITA: All right. Well, I don't think we...

Dr. SLAMON: I think that...

Dr. DeVITA: I beg your pardon because we haven't been wrong. If you really look at the survival statistics and the mortality statistics, you'll see that the people who were very pessimistic about setting the time lines in '74--they were wrong because they predicted a straight line increase of incidence in mortality.

Now let me just draw a parallel between what you just said. We went from a 33 percent survival rate to over 50 percent using the old therapies where you had to fly blind. Now we have all those targets you mentioned, and we have the capability of synthesizing chemicals to attack those targets. I think there's every right to believe that there'll be accelerated process. Of course, we don't know when that's going to happen.

Dr. GROOPMAN: That's my point.

Dr. DeVITA: But I think you're going to see more Gleevecs and more approaches likes Gleevec, just like you've see more monoclonal antibodies come out that are very specific for certain targets. I think it's paying off. And the mortality rate decline that was noted in 1990 for the first time has been increasing in its decline every year. So we're seeing a...

Dr. DRUKER: This is...

Dr. DeVITA: You know, I think that's a reason for saying we can set targets. And if we set programs in motion to reach those targets, we can reach them. And we did.

FLATOW: Dr. Druker.

Dr. DRUKER: Brian Druker from Portland. I think the two aren't really all that far off. And I think that Dr. Groopman has said time and again, 'This is a time of great hope.' And when I go around the country and give talks, there are a couple of things that I try to emphasize. The first is--as everyone has said--this is decades of cancer research paying off. And although we're not announcing any time lines, we all recognize that there's still a lot of work to be done. We're at an incredible period of opportunity. With the genome being reported, we have all the pieces of the puzzle. We didn't have to figure out how they all fit together, what parts are broken. We know we're on the right track with the examples of Herceptin and Gleevec.

And so although we can't announce time lines, we know that the efforts we put into this are going to begin to pay off. And the people get that after I give a talk will come up to me and say--will thank me for my work. And they'll say, 'I have a loved one with a specific type of cancer. And I know that you can't help them today, but you give me hope for the future.' And that, to me, really brings home the point, or the message of hope.

FLATOW: Mm-hmm.

Could one of the reasons that we may be seeing--without putting any blame on anyone's shoulders, one of the reasons we could--may be seeing an optimism on these statements coming in the media that you've been talking about be that--as opposed to 30 years ago when we had the war on cancer that was declared, right now we have so many researchers doing so much--you know, doing so much research with private companies and there's so much of the stock market locked up in this so that any kind of word about a new, possible cancer cure drives up the price of stocks, and possibly the fortunes of the people who work at these companies?

Dr. DeVITA: Well--this is Vince DeVita. I don't think most people I see quoting--saying these things in the press, I don't see them doing that for purposes of driving up the stock. However, I do think there is hype, and we all worry about it. And I was saying the other night when we talking about this on "The Charlie Rose Show" that there is a difference between proof of principle in a human being--which is what Brian Druker has done with Gleevec; we have human beings receiving a specific agent against a specific target and the disease going away--and proof of principle in an animal model. And sometimes the press doesn't draw a distinction. So somebody does something that's glorious in mouse and say this is going to be glorious for humans--there is not a one-to-one relationship between a mouse and a human.

And so I sometimes think the hype comes from not sorting the two out. And we don't see too many things like what Brian did, and that's worthy of all the optimism we could bring to it.

Now the classic stock market run-up, I guess, was the business of the angiostatin and the pronouncement by Dr. Watson that cancer would be cured in two years. I--you know, I love Dr. Watson and he's a good friend of mine except he knows nothing about cancer. His Nobel Prize was something quite different. And I think the press couldn't resist quoting a Nobel laureate on the basis of a mouse model. And that was--you know, that drove up stock; it drove up hopes. And I think the field that he was talking about will be very valuable, but that was a sample of the wrong portrayal...

FLATOW: Oh, Judah Folkman's work?

Dr. DeVITA: Yeah. Yeah, that's right.

Dr. GROOPMAN: I think there's another proof of principle. First, you know, Vince, I don't think it's fair to say I'm pessimistic, because I'm not, and I think the disagreement really has to do with how soundbites are presented in the media, how careful we all need to be in terms of setting time lines. Let me just finish.

Dr. DeVITA: Well, I'm sorry, Jerry, but you mis-cite the data, so I think that's pessimistic.

Dr. GROOPMAN: First of all, in 1971, as you know, there was a unanimous resolution passed in the Congress that cancer should be cured by 1976. Now you said the premises were wrong and it was ridiculous and so on, but nonetheless, that's the way it was presented to the public and to the Congress. Now the...

Dr. DeVITA: And so for you, it'll always be a failure because it just wasn't cured by 1976.

Dr. GROOPMAN: No. No, wait. Let me just finish. In the 1985 projections, there's no doubt that the cancer mortality rates started to fall in 1990 and have fallen. The belief is--and the data, as you know, are not yet in for 2000--that the primary reason for that, which I celebrate and you celebrate, is mammograms to detect early breast cancer, colonoscopy for early colon cancer or polyps, Pap smears and some impact, perhaps, likely of adjuvant chemotherapy. But for people whose cancer has...

Dr. DeVITA: Fifty percent of it.

Dr. GROOPMAN: ...spread beyond the primary site, metastatic breast cancer, the reason that Dennis Slamon's study was hailed as a landmark in the New England Journal was because it was one of the few or perhaps the only example of extending life significantly, which was five months in the New England Journal, and now with more accurate, you know, fiche data identifying patients better, nine months or so, Denny, if that's correct.

Dr. SLAMON: Those are correct, yes.

Dr. GROOPMAN: OK. And so I think it's very important to give patients and the public an accurate understanding when we talk about curing cancers. We do a very good job with surgery, chemotherapy and so-called adjuvant chemotherapy in a very early stage. But when cancers have spread widely, we have not made major impacts.

Dr. DeVITA: Jerry, what percentage of breast cancer patients do you think present with early stage?

Dr. GROOPMAN: I think now, a large number, perhaps the majority.

Dr. DeVITA: Ninety, 95 percent, so that the work that is going on to show that you can use adjuvant therapy and using it at an earlier stage has had a major impact on survival, so...

Dr. GROOPMAN: We're not disagreeing about that. But what I'm saying is that the modalities of treatment--that early detection is what has made the major impact.

Dr. DeVITA: Fifty percent of the reduction is early detection.

FLATOW: OK. Let me just jump in because I think we've gone through this ground. I'm fascinated by Dr. DeVita's reaction because it's--Dr. DeVita, it almost seems to me, as just someone who's listening, this is something personal with you.

Dr. DeVITA: Well, you know, I've listened to it for about 25 years and I think the article...

FLATOW: So you take it so personally.

Dr. DeVITA: I was formally the director of the National Institutes...

FLATOW: Oh, I know. I used to cover you as a reporter.

Dr. DeVITA: And I think people mis-cite the data. And it's a mantra that the war on cancer--because it violated some very fine rules, like, for example, money can't buy ideas; therefore, the war on cancer was wrong. Actually, money does buy ideas, and it bought a lot of ideas by putting a lot of people to work. So what I see is a sort of reactivation of an old argument that was wrong then and is wrong now. And I think there are various people around apparently willing to get up and say, 'This is what's happening,' and I prefer to say it. So, yes, I have an interest in the war on cancer. And I think--I like Dr. Groopman, but I think his article could have been written in 1974. I don't think it accurately cites the mortality data, and I think it's too pessimistic. You can say I'm optimistic, but the article is pessimistic, the way I read it, so...

Dr. GROOPMAN: Well, if you read the end of the article, it says that we might decrease the mortality rate for melanoma or lung cancer or lymphoma, say with Rituxan, or with breast cancer by 50 percent or 90 percent or zero in the next 10 years. We don't know. And...

Dr. SLAMON: Jerry, this is Dennis...

Dr. GROOPMAN: Yeah.

Dr. SLAMON: ...in Los Angeles, and I'll be the one that'll go out on a limb here. No one would be foolish enough to give numbers or time lines or dates. But I think that, unless I've really misread what's going on in the field and what we're seeing in terms of what's happening, including some of the data that aren't even yet publicly known, as they're being developed, that there's little question that we're going to impact on metastatic cancers, the major epithelial cancers--lung cancer, colorectal cancer, prostate cancer and breast cancer--with these new therapies. I can't--and no one should--give time lines or anything like that. But I can't believe anyone who really knows the data could feel that there isn't going to be a dramatic impact on these numbers within the next five years.

Dr. GROOPMAN: Within the next five years.

Dr. SLAMON: Yes.

FLATOW: All right. Let me remind everybody that this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News.

And let me see if I can get a phone call in here. Spencer in Portland, Oregon. Hi, Spencer.

SPENCER (Caller): Hello there.

FLATOW: Hi there.

SPENCER: I'm looking at a letter that was faxed to me in February of 1997 from an actuary who worked then for Standard Insurance here in Portland, Oregon, a gentleman, name of Robert Mayvor(ph). And in '89, Mayvor was requested by the CEO of a large insurance company to investigate a targeted therapy that was being used at that time, which they believed to be, from what they had heard from mainstream sources, such as the ones you have on your panel there, to be fraudulent. And he made 12 visits to this man's clinic, three of which he had an oncologist in tow. They reviewed cases, etc., etc., and on the basis of the investigation, he recommended that the--I'll just quote from the letter, "Our company concluded that Dr. Brzezinski(ph) work was one of the more promising new approaches to cancer and we agreed to pay for the treatment." I should add that this was a formal review process conducted by our medical review board whose members included two MDs, a lawyer, the VP of claims and me.

They also went behind the scenes subsequent to that to get the National Cancer Institute to send a team down to this man's clinic, which they did, came back with a very favorable review involving seven cases of brain tumors, and this therapy, which is called anti-neoplastin, is especially effective against brain cancer. It is the only therapy to ever show results in medulla blastoma, a particularly deadly form of brain cancer in children.

FLATOW: Spencer, is there a bottom line, because I'm running out of time here?

SPENCER: Well, you know, there's a double standard here, gentlemen.

FLATOW: You're saying that this was not approved, this therapy. Is that basically what you're saying? Why was this not approved?

SPENCER: The FDA has sat on this for 25 years. They sit on it to this day. It is non-toxic. It is targeted. It works. And, of course, it threatens a $ 13 billion chemotherapy industry, which is the problem, and I wanted the American people to know about it.

FLATOW: Dr. DeVita, any comment, someone who sits...

Dr. DeVITA: Oh, yeah, it's been investigated by a lot of people, and I think as stated by your caller, it doesn't pan out that way. Certainly, you know, the Cancer Institute has offered to conduct a study with Dr. Brzezinski, and it's not easy to get the studies done. So I have not, you know, looked at the data myself, but I don't think it's as cut-and-dried as your caller makes it. By the way, there are therapies that work in medulla blastoma quite well, thank you. It's not the only one, if it works in medulla blastoma.

Dr. SLAMON: This is Slamon again. That's number one. Number two, the issue of there being a double standard, I couldn't disagree more. The problem that many people who are making claims for any of a number of approaches are wanting is--what they're wanting is a double standard. In other words, they don't want to hold their approach up to a randomized controlled trial that would answer the question. Remember Laetrile. When the NCI finally was able to pull off a randomized controlled trial, that treatment that was touted very much like what you just heard was shown to be essentially ineffective.

FLATOW: So you're all...

Dr. DeVITA: But we did test it, however. And we did...

Dr. SLAMON: It was tested, yes.

Dr. DeVITA: We did test it. It wasn't easy to get it done, and I don't think that it's been easy to get Dr. Brzezinski to participate in a randomized trial as well. So...

Dr. SLAMON: I agree with you.

FLATOW: But you would welcome his participation if he did?

Dr. DeVITA: I certainly would.

FLATOW: OK.

Dr. DeVITA: I was the one who started the Laetrile trials, so...

FLATOW: All right. We're going to take a quick break and come back and talk lots more about cancer research and take more of your questions.

Just a reminder, we cannot give you personal advice when you call up about your own--it's unethical and we say this all the time when we talk about medicine, please don't ask our guests to prescribe medicine or give you personal advice. I'm sorry. We just can't do it. But any general questions about cancer, we'd like to have them from you. Stay with us.

I'm Ira Flatow and this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News.

(Announcements)

FLATOW: Welcome back to TALK OF THE NATION/SCIENCE FRIDAY. I am Ira Flatow.

A brief program note. With a review of US defense policy taking longer than expected, Juan Williams will talk to a host of military and defense experts about what could be in store. And that's on the next TALK OF THE NATION on Monday in this hour from NPR News.

We're talking today about targeted cancer drugs and other cancer research with my guests, Dr. Vincent DeVita, director of the Yale Cancer Center; Dr. Brian Druker, professor of medicine, director of the Oregon Health and Science University Leukemia Center in Portland; Dr. Jerome Groopman, chief of experimental medicine, Beth Israel Deaconess Medical Center and professor of medicine at Harvard; Dr. Dennis Slamon is director of Revlon/UCLA Women's Cancer Research Program at the Jonsson Cancer Center at University of California-LA. 1 (800) 989-8255.

Let me ask you, Dr. Druker or anybody else who wants to chime in, with the strides being made in the Human Genome Project, all kind of things, is it now as simple as finding the targets on these cancer cells, of where the cancer cells go bad and making a magic bullet that goes right to it? Is it pretty simple? Is an engineering feat now?

Dr. DRUKER: In some respects, yes, but there are two engineering feats. First of all is figuring out what the targets are, and the second is designing the drugs to attack those targets. In some cases, that's going to be simple. In other cases, that's going to be a very tricky engineering feat. And in some cases, we may not yet even have the technologies to design some of those drugs.

FLATOW: So...

Dr. DRUKER: But as we peer into the future, I think that those are going to become more technological issues, rather than trying to get the tools to develop these reagents.

FLATOW: Well, what made--and you can all join in--what made it easy to happen with Gleevec? Why could you do it--I'm not saying--'easy' is the wrong word. Why were you successful in doing it first with Gleevec and working on that kind of cancer?

Dr. DRUKER: Well, actually, it wasn't easy. First of all, you had to identify the target, and that took pretty close to 30 years before people started to work on it. The reality is that that time frame can be accelerated with the Genome Project and other advances. Then there was a huge amount of skepticism that you could design a drug just to target this one enzyme. This enzyme is a family that has about two or 300 different members.

FLATOW: Right.

Dr. DRUKER: And there's huge amounts of skepticism that you could target just one or two of these enzymes. That was actually possible to do, and this sort of disproved that hypothesis that it wasn't going to be possible. But that project took between five and eight years. Then you've got to test the drug, show that it would work, formulate it for clinical trials, and then do the clinical trial. All this takes time.

Dr. DeVITA: Ira, if I could jump in, too. I think there was one feature of chronic myelocytic leukemia that is different than other tumors, and that is the target is probably the only major target, where if you take a tumor like cancer of the pancreas, I could list five potential targets. So one has to either be able to find the target amongst those five that's critical or if you have to block all of them, then you're going go have to develop five compounds for cancer of the pancreas, not just one. So it gets more complicated with some of the more common tumors.

The other point I think, though, we're facing--and I made this point the other night, and it's a point that interests me a lot--and that is that we do have the capability of synthesizing chemicals against identified targets. We have more targets and more chemicals than we have the ability to study in clinical trials. And so that a very mundane problem is going to stop us from moving as fast as we'd like, and that is the ability to test all these things in humans. If you want five-year survivals, you have to wait five years. And so you'd better start a lot of studies soon, and then fill them up fast so you can get data quicker. And so we have an embarrassment of...

Dr. GROOPMAN: May I agree with you then?

Dr. DeVITA: Yes, indeed. I'd love it, Jerry, if you could. We have an...

Dr. GROOPMAN: Yeah. Well...

Dr. DeVITA: ...embarrassment of riches.

Dr. GROOPMAN: Yeah. Well, I think there are two things. I think Vince's point is very important in terms of the uniqueness of myelogenous leukemia, which we all agree. I mean, you know, you look at the benefit of Herceptin, you know, which is clear, and as I said before is a landmark in terms of the state of the field of treatment of breast cancer. When you have multiple drugs, it does become more complex.

What I think's interesting about the story of Gleevec, too, is we still have difficulty predicting from the test tube or even from animal models how drugs behave in people. And if I recall correctly from Brian Druker, you know, there was concern that Gleevec would cause--did cause significant liver damage in dogs, and there was questioning whether it should even come into clinical trial. So I would echo what Vince says, and that is that clinical trials are key ultimately--you know, this sort of acid test of the impact. But I think, again, it's not a question of pessimism. It's a question of what Harold Varmus called guarded optimism. Because I think that there's a lot of opportunity for failure, and failure is an intrinsic part of the success of science.

Dr. DRUKER: This is Brian Druker from Portland. One of the things that I think brings together some of the comments that both Dr. Groopman and Dr. DeVita have made is that Dr. Groopman is talking about some of the major advances being made with early detection and then Dr. DeVita talked about some of the difficulties in treating our most advanced cancers. But as we move into the future, I think it's likely that as we understand what some of the critical early defects, abnormalities in cancer, that we'll also learn how to detect cancers earlier when they're simpler. And so that, in fact, it should become even easier to treat cancer in its earliest stages not only by understanding the specific abnormalities early but also by detecting earlier.

FLATOW: Dr. Groopman, you pointed out in your article that the war on cancer was a failure because it's slated as a war, and it should not have been slated as a war on cancer. Were enough people burned--and I mean, congresspeople who were in charge of funding and basic research funding--were enough people and are enough people burned by that failure that they are now shying away from investing money that might be funded in...

Dr. GROOPMAN: No. I think that there should be more money now going into cancer research and into ancillary fields, like chemistry and physics and computer science, which will accelerate the development of these drugs using, you know, sophisticated design and so on. My point was that the idea of a war, first of all, sets up, you know, this sort of metric of victory or defeat. It also thinks of cancer as a single entity, which it's not. It also, contrary to what Vince said, where he says I'm rehashing an argument that was a failure--it was a tremendous success. It led to the benefits in terms of AIDS. We would have never been able to reduce the mortality rate in AIDS by 90 percent if we didn't have the tools and technology that came out of that effort...

Unidentified Panelist: Hear! Hear!

Dr. GROOPMAN: ...and the whole biotech industry. But I don't think we need a war to make progress against cancer. I think that we have to change the rhetoric. I think what we need is discovery, and I think discovery is unpredictable. And I think that giving the opportunity to have as much freedom and creativity and innovation and questioning of conventional wisdom, that's not the kind of mentality that occurs during a war.

Dr. DeVITA: You know, this is Vince DeVita. I agree with Jerry, actually. I think that we're stuck with the designation 'war on cancer.' That was a label that was applied by laypeople who used it to influence Congress to start the whole process, and I think it both paid off, because it increased the funding for cancer research and all research, and it also backfired in the sense that it implied that there was a beginning and an end. There isn't a beginning and an end. You have to just understand what the end points are. I wish we could get rid of it as a label, but not the effort.

But I would point out, by the way, Jerry, though, that Ira just said in your article, you pointed out that the war on cancer was a failure. So I don't think I was the only one who interpreted that...

Dr. GROOPMAN: Well, I don't know if that's a direct quote from my article. What I said was there were--you know, it fulfilled the law of unintended consequences, and I quoted Rick Klausner, who I think has been correct about this, in terms of changing the metaphor; that it's time to call off the war. And certainly, as you say--and, you know, I'm not going to hold you, Vince, responsible for what happened in 1971--but the idea that there was going to be, you know, an imminent cure for cancer, which is what Sydney Farbert(ph), you know, and the whole momentum that led Congress to do this, a unanimous resolution in the House of Representatives and the Senate to cure cancer in five years is really not obviously correct or fair to the public.

Dr. DeVITA: But that was not correct, no.

Dr. DRUKER: This is Brian Druker. I think we have to be very careful--and Dr. Groopman has already mentioned that we need to increase cancer research funding. If we're going to make progress, there has to be progress on several fronts. We need more funding for cancer research, and I don't want to take away optimism about the progress we've made and the tools we've collected and in the amount of work that's left to be done. And so if we use words like 'Let's call off the war'...

Dr. DeVITA: Yeah.

Dr. DRUKER: ...I start to think of, 'Well, then we're done? What's happened?'

Dr. SLAMON: Yeah.

Dr. DRUKER: I want to increase the effort...

Dr. SLAMON: This is Dennis. I want to...

Dr. DRUKER: ...in terms of research, and I think it's critically important that that message get through.

FLATOW: Let me go to the phones. Let me go to the phones, get a call in before--we're running out of time. Cathy in--is it Salmouth, Mass--Falmouth?

CATHY (Caller): Yes.

FLATOW: Go ahead.

CATHY: Hello?

FLATOW: Yes. Go ahead.

CATHY: OK. I find it very hard to listen to a show on cancer without even a mention in almost an hour of the toxins in our environment and all the things that people can do to cut their chances, keep their bodies--their organs healthy by not eating chemically laden foods, not taking your clothes to the dry-cleaner. I think you know all the fa--you've heard it before.

Dr. DeVITA: And, of course, not smoking.

CATHY: But that certainly is a factor in cancer. As a matter of fact, the men that did the gene mapping were asked the very question that Ira just asked the guests. Could we just manipulate genes and cure cancer? And their answer was that cancer is 90 percent, I think they said, an environmental disease. It's caused by the toxins that come into our bodies. So if Congress could pass some laws to clean up the air, get the pesticides out of the lawn and all the various things--I mean, as you people are curing cancer, Monsanto is ladening all our soybeans with Round-Up Ready, and everybody is eating them in their (technical difficulties) and their taco shells and everything else. This is a serious thing. If we could clean up the environment, we could do a huge step towards getting rid of cancer and keeping people healthy so they can fight it off or even if they're cured--I know people that have been cured because they were healthy to start with, a much better chance.

FLATOW: All right. Let me get a reaction, but f...

CATHY: I want to hear the comments, please, and also there are...

Dr. DeVITA: Yeah. This is Vince DeV...

FLATOW: All right. But first, before--Dr. DeVita, I have to remind everybody first that this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News. Sorry. Go ahead.

Dr. DeVITA: No. I was going to say I certainly don't disagree. We didn't talk about prevention here, and that's a whole new field. We've been talking about other areas. But I would point out that 33 percent of all cancers are caused by cigarette smoking. At the moment, the best estimate for cancer causation by chemicals is about 7 percent. Very important, but still not like cigarette smoking, and I'm a little surprised--and I hope the caller wasn't a smoker--that in terms of cleaning up the environment, there wasn't some mention of cigarette smoke.

FLATOW: Is that a change in statistics?

Dr. DeVITA: No.

FLATOW: Because we used to hear years ago that environmental causes--and I don't mean environment meaning nature...

Dr. DeVITA: No. Yeah.

FLATOW: ...but environmental causes were so much a high part of cancer...

Dr. DeVITA: No. It was always a part. The rest of the...

FLATOW: ...that there were co-factors they used to talk about, yeah, the environment is...

Dr. DeVITA: Yeah. The rest of the environmental causes are internal hormone changes, things of that sort. But the figure 7 vs. 33 percent has always been that part of it. About 70 percent of all cancers can be called environmental, but 33 percent of cancers are caused by smoking and 7 percent by chemical. So it is...

FLATOW: So you would not agree that pesticides and things that she was talking about were contributing to...

Dr. DeVITA: They are. But they're not the great majority. Certainly, if you had to make one step, you'd stop smoking, and you'd reduce mortality from cancer by a lot.

Dr. DRUKER: Ira, this is Brian Druker. I think as you look to cancer therapies, you've got to look to a broad-based approach. You've got to look to prevention, early detection, specific targeted therapies like the ones we're talking about today, and also modulation of the immune system. You've got to talk about a whole package, but we're talking about targeted therapies today.

Dr. SLAMON: This is Dennis Slamon. I just want to add in to what Brian just said and sort of what he said earlier. I think that when we talk about these targeted approaches and identifying what's broken, that doesn't preclude the concept of preventative approaches. As we understand what's broken and we understand how things get broken, we begin to understand how to prevent that breakage from occurring. Having said that, there is one thing that is inescapable in this, at least as far as I know the data. The other areas of medicine have done quite well in improving survival, infectious diseases certainly being first and foremost among...

FLATOW: I've got 10 more seconds. You're going to have to hurry up and...

Dr. SLAMON: Sure. And people are getting older, living longer, and that's good. But DNA damage and problems that happen with genes are going to happen with prolonged age, and we are going to see cancer that is going to stay with us.

FLATOW: All right.

Dr. SLAMON: It's a matter of approaching it better.

FLATOW: All right. Thank you very much. We've run out of time. I'd like to thank my guests: Dr. Dennis Slamon, director of Revlon/UCLA Women's Cancer Research Program at Jonsson Cancer Center at UCLA; Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center, professor of medicine at Harvard; Dr. Brian Druker, professor of medicine and director of the Oregon Health and Science University Leukemia Center in Portland; and Dr. Vincent DeVita, who is director of the Yale Cancer Center. Thank you all for joining me this hour.

(Credits)

FLATOW: If you'd like to write us, please send your letters to TALK OF THE NATION/SCIENCE FRIDAY, 1 Center Street, New York, New York 10007. Or for faster delivery, you can always surf over to our Web site at sciencefriday.com, where you'll have links to all the topics and you can leave us e-mail there. From NPR News in New York, I'm Ira Flatow.

Source: National Public Radio

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