FROM MICE TO MEN?
May 4, 1998
Researchers have found that a combination of drugs, endostatin and angiostatin, successfully shrinks cancer tumors in mice. Is this a step towards a cure for cancer? Jim Lehrer discusses the findings with the man who will oversee the clinical trials of the drugs in humans, Dr. James Pluda of the National Cancer Institute.
JIM LEHRER: Today's cancer story has become a business, as well as a medical development. On Wall Street today, the stock of a pharmaceutical company called Entremed soared on news of a promising cancer treatment, which it has the rights to. That research is based on work done at Boston Children's Hospital, which found two drugs used in combination completely eliminated cancerous tumors in mice. For more on those findings, Dr. James Pluda of the National Cancer Institute. He will oversee clinical trials of the drugs in humans.
A RealAudio version of this segment is available.
April 13, 1998
A study has shown that daily cigar smoking can cause cancer and heart disease.
March 18, 1998
Vitamin E is thought to be a potential weapon against prostate cancer .
March 12, 1998
The director of the National Cancer Institute discusses the declining numbers of certain cancers .
Browse the NewsHour's coverage of Health.
The National Cancer Institute.
DR. JAMES PLUDA, National Cancer Institute: Thank you, Jim.
JIM LEHRER: In simplest of terms, what exactly did that research in Boston find out?
New findings in the fight against cancer.
DR. JAMES PLUDA: Well, these are drugs that we call angiogenesis inhibitors. That means that they block the formation of new blood vessels by tumors. And what they were able to show with these drugs was that they were able to stop the tumors from forming blood vessels; they were actually able to get the new blood vessels that had been formed to go away, and actually shrink large tumors in mice all the way down to very small microscopic tumors that could not be seen with the human eye.
JIM LEHRER: And how was it possible that they reduced the blood vessels in the tumors but didn't reduce the blood vessels in the nearby good stuff as well?
DR. JAMES PLUDA: Well, in people--in the adults anyway--the blood vessels generally are no longer replicating; they're no longer forming new blood vessels. There's only a couple of instances in adults--adult mice and adult people--where new blood vessels are formed. Those are in wound healing, in the female reproductive cycle and also in fetal, baby developments. So these drugs did not have any effect on already established blood vessels, that is, on old blood vessels that are already there, these drugs don't do anything. They only affected the brand new blood vessels that were being formed by the tumor cells.
JIM LEHRER: Now, these two drugs, are these drugs that just came out of nowhere? Were they developed specifically for this purpose? Tell us about that.
DR. JAMES PLUDA: Well, these drugs came through Dr. Judah Folkman's lab. He's been working on angiogenesis for really 30 years and is really the father--the godfather of this field. And he's kept the field alive. He made an observation that in some people--not all-but in some cases--mainly in patients with breast cancer patients had presented with very large masses in their breasts--of tumor masses--but they didn't have any evidence of disease anywhere else. When the surgeons took these masses off, within a short period of time--many instances only months--these patients had tumors that had spread all over their bodies. And what he felt--what he thought was that those tumors were probably there already but they were very small, microscopic, dormant tumors that just weren't growing, and that somehow the big tumor was making a substance that was stopping them from growing, and he felt that this was probably a substance that blocked the blood vessel formation. He then found in mice a tumor that did similar things, looked for one of these agents that was circulating in the mice, and discovered angiostatin. And what angiostatin is, it's simply a fragment of a normal protein, of a normal molecule that's found in blood that the tumors are able to make.
JIM LEHRER: And can it be made artificially into a drug?
DR. JAMES PLUDA: Yes, it can. And, in fact, right now the National Cancer Institute is working on angiostatin with Bristol Myers Squibb and on endostatin with Entremed to make these drugs so that we can then take them into clinical trials in people.
JIM LEHRER: All right. I want to talk about that. Dr. Folkman said up to this point the only thing that he has proved is that if you're a mice, I can get rid of tumors.
DR. JAMES PLUDA: Right.
From mice to men: what does this research mean for human patients?
JIM LEHRER: But if you're a human, relax a moment. Tell us now--you're the man that's in charge of now finding out whether this works--is going to work on humans. How are you going to go about it?
DR. JAMES PLUDA: Well, the first thing that we'll do is we'll secure a drug supply. Once we--
JIM LEHRER: Is that going to be easy to do?
DR. JAMES PLUDA: Well, it's not an easy process. Proteins are not always easy to make, especially if you have to make large volumes of them, but I think it's doable. We've been working very hard with the companies. The companies have been working very hard. And we honestly think that we'll have endostatin possibly in the clinic in about a year from now. The first thing that we'll do is we'll take these drugs and we'll try them out in what we call "early clinical trials" or "Phase I trials." Those are studies where we first give these drugs to people to try and find out a little bit about how the drugs react in people, how the people respond to them in terms of--
JIM LEHRER: These will be people with tumors?
DR. JAMES PLUDA: These will be people with advanced cancers.
JIM LEHRER: And how will it be administered--something you take through the mouth, or is it injected, how?
DR. JAMES PLUDA: Well, these drugs will have to be initially injected by vein.
JIM LEHRER: I see.
DR. JAMES PLUDA: Hopefully, we'll come up with a way to give them maybe by injection under the skin, or even with pills.
JIM LEHRER: Okay. You're going to select--you know how many people?
DR. JAMES PLUDA: No, we don't know at this point.
JIM LEHRER: But it could be hundreds, right?
DR. JAMES PLUDA: Well, the initial trials won't be that large.
JIM LEHRER: I see.
DR. JAMES PLUDA: What we'll do is we'll start out with small amounts of drug and give it to people, see how they do, and they slowly escalate, increase the dose of drug that we're going to be given is we need to find out how people handle the drug, how long it lasts--
JIM LEHRER: Side effects and that sort of thing.
DR. JAMES PLUDA: Side effects and those things. And then we also need to determine what dose of the drug in people--because we have no idea--that we think will work--and then move into the other trials.
JIM LEHRER: This is clearly in public terms at least a major development. Why is it going to take a year for you to start using this drug on humans?
Why does it take so long to test the drugs on humans?
DR. JAMES PLUDA: Well, it's the production facility, making the drug is really the biggest hurdle that we have today to get the drug into the clinic. It's very simple in the desk--on the desktop on somebody's laboratory to whip up a little batch of drug and give it to mice. It's a whole other thing to make the drug pure enough that you can--and in large enough quantities that you give it to people the last thing we want to have happen is that we start chemical trials, we have people benefitting, and we run out of drug, and have to stop giving it to them.
JIM LEHRER: What are the side effect potentials here, or are there any--are they any known ones at this point?
DR. JAMES PLUDA: Well, in the mice so far Dr. Folkman has reported that he hasn't seen any side effects. The things that we do worry about are stopping the normal processes in people where blood vessel formation is needed, that is, stopping wound healing if you cut yourself or, more importantly, if you have surgery. We're concerned about that. Now, we don't know whether this drug will affect those processes, but it's a worry in terms of its effects on normal female cycles and also its effects on fetuses and unborn children.
JIM LEHRER: What word would you use to describe, what series of words would you use to describe what this development is and means?
DR. JAMES PLUDA: Well, I think what we found--it's something that we haven't seen with cancer drugs before in mice. I think if the data holds when we move it into people, if it looks just as good as people, I think it will be a big step forward in our fight against cancer, but that's a big "if" right now. There are lots and lots of drugs out there that cured mice that when we gave them to people didn't have anywhere near the same kind of effects.
JIM LEHRER: Does this seem different than those, however, in some ways?
DR. JAMES PLUDA: Yes. This does. Most of the drugs that we've used in the past have basically been against the cancer cells, themselves, the chemotherapies that we tend to use. Now, one of the problems with those is they also affect normal cells and make you very sick. But the cancer cells have found a way to become resistant to them, to sort of overcome the effects. These drugs don't go after the cancer cells; these drugs go after the blood vessels. And the blood vessels come from normal cells. So Dr. Folkman's shown that there may not be resistance. We haven't seen really any major side effects. And they've been able to reduce these tumors down to these little microscopic pinpoint tumors, and that alone is different from what we've seen with most other drugs.
"Most of what we do is cut the dandelion off. And as you all know, you cut the dandelion off, it keeps growing back. These drugs go after the roots."
JIM LEHRER: Dr. Folkman used an analogy in one of the interviews of grapes on a vine. And he said the chemotherapy and the normal treatments treat the grape, in other words, the tumor.
DR. JAMES PLUDA: Right.
JIM LEHRER: And these drugs treat the vine.
DR. JAMES PLUDA: Right.
JIM LEHRER: Would you agree with that analogy?
DR. JAMES PLUDA: Yes. I would. I tend to use other gardening analogies, such as dandelions in your lawn. Most of what we do is cut the dandelion off. And as you all know, you cut the dandelion off, it keeps growing back. These drugs go after the roots. These drugs actually go after the roots of the plant. And the plant, the whole plant dies.
JIM LEHRER: We know when the trials are going to begin. Once the trials begin, is there any way to put some kind of scenario, some kind of time to how long it might be before we know whether these things work.
DR. JAMES PLUDA: That's very hard because we don't know what we're going to find. If we find--
JIM LEHRER: But say everything goes the best possible way.
DR. JAMES PLUDA: Everything goes the best possible way, I would hope that within several years these drugs would be available by prescription.
JIM LEHRER: Several years?
DR. JAMES PLUDA: Well, yes. The trials themselves take time because you have to get the patients on the study, give them the drugs for prolonged periods of time, and then see how that works. And we normally do--after we do the initial trials, we'll set up some trials, and some of the trials can take years to get the patients on and follow the patients for a year or more just to see if the drugs are having their effects.
Prognosis: "cautiously optimistic."
JIM LEHRER: One of the great terms in Washington in the political world is "cautiously optimistic." Is that what you are tonight?
DR. JAMES PLUDA: Yes. I've used that term before.
JIM LEHRER: It works in medicine too.
DR. JAMES PLUDA: It works in medicine too, yes.
JIM LEHRER: All right, Doctor. Thank you.