Week: 550.1 Guest: Dr. Henry Brem, Dir., Neurology and surgical oncology, Johns Hopkins Hospital, Baltimore, MD Topic: Shark substance drastically slows tumor blood vessel growth Producer/Host: Steve Girard

NEMA: Researchers at Johns Hopkins Hospital are excited by the promise of a substance which helps control cancer by cutting off a tumor's blood supply....a hormone-like chemical found in the liver of a shark. Here to talk with us about it is Dr. Henry Brem, Director of surgical oncology at Hopkins.....

BREM: Squalamine is very active against cancers in the laboratory. It's a unique compound in that it's a steroid with antibiotic activity. And it was discovered to inhibit blood vessel proliferation and therefore control tumor growth. We're very excited about its potential, although it has a distance to go before its in clinical trials.

NEMA: Can you explain the relationship between a cancerous tumor and blood vessel development, why is it important to the tumor, and what does it mean for researchers...?

BREM: Well, Judah Folkman at Harvard first described in the mid-1970's that tumor cells were dependent on eliciting a special blood vessel response in order to proliferate, and that if you stopped that abnormal blood vessel proliferation, you essentially starve the tumors. And there's been much work over the past few decades trying to develop compounds that selectively inhibit the angiogenesis, and therefore cause the blood vessels to stop proliferating, and therefore, essentially starve the tumor and allow it to be killed by doing so, or at least to be controlled by doing so. Squalamine is a new class of drugs, a new type of drug that tries to achieve that goal.

NEMA: I understand squalamine is still in the animal testing phase...how has that research turned out?

BREM: Right. We've been looking at brain tumors in animals and found that there's a marked improvement in survival and diminishment in the size of the tumors by treating with squalamine. So we're encouraged by that and there are a number of hurdles that yet need to be overcome before it can be tested clinically, but we're working very rapidly towards that goal.

NEMA: How does squalamine fit in with other cancer treatments and drugs...have any clashes shown up yet...?

BREM: Well, we have looked at that issue...that's a very important one for, what effect it'll have on patient treatments. And in the laboratory, it appears to be synergistic, to improve the benefit of chemotherapeutic agents. So it may be that a combination of inhibiting the blood vessel proliferation and treating with chemotherapy may be the most powerful approach to treating cancer. Beverly Tiescher at Harvard has shown, together with Judah Folkmann and his group, that the combination of the anti-angiogenesis and chemotherapy is extremely powerful. So, there's a lot of work going on the try to explore both in parallel as mutually complimentary treatments.

NEMA: Dr. Henry Brem, Director of surgical oncology at Johns Hopkins Hospital. Other investigators are checking for effects of shark substances on other human diseases. Squalamine apparently does no harm to normal, healthy cells. The drug may be used in clinical human trials sometime next year. I'm Steve Girard.