University Communications

Fall 1998
The Culprit is Cancer
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In 1990, Slamon set out to answer the next critical question about HER-2: Was the defective gene causing the deadly tumors, or was there something else? To find out, the researchers injected normal human breast cells with HER-2. "Sure enough," says Slamon, "the cells grew more rapidly and they behaved in a more malignant fashion." The experiment was repeated using mice; the results were identical. Slamon had proved the link between HER-2 and breast cancer.

There was one last piece of the puzzle to solve: Could the researchers find a way to target HER-2 and mediate its apparently destructive effect? Slamon developed antibodies, called in others from academic and commercial pharmaceutical labs and began methodically testing them on tumor cells. After a dozen or so attempts, he tried Herceptin, an antibody manufactured by Genentech. It worked.

"Not only did it work on the HER-2 cells," Slamon says, "but when we tried the antibody on cells that didn't have the alteration, it had no effect. That was great news: The antibody was specific, unlikely to affect cells without this alteration. And in mice, exactly the same thing happened. Herceptin stopped the growth of the tumors." Now that the antibody had been proven effective in the laboratory, Slamon and Genentech went to the FDA and received permission to begin testing the drug in women with advanced breast cancer.

The odds against Slamon succeeding were still huge. As the UCLA researchers entered Phase I of the Herceptin clinical trials, there were plenty of scientists, many at Genentech even, who remained skeptical. Never before had an antibody been shown successful in cancer treatment.

But Slamon's instinct triumphed again: The early studies proved Herceptin to be relatively safe. In the summer of 1995, the critical Phase III trials began. Eventually, 940 very sick, very hopeful women participated in the breakthrough study at more than 120 institutions around the world.

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