February 2003

Personalized Medicine's Bitter Pill

Continued from page 1

By Stephen S. Hall

Bumpy Road

Given the uncertainties, those starting down the road of personalized medicine could well learn from Genentech, the South San Francisco, CA, biotech pioneer, and its experience creating a cancer drug called Herceptin. Few people made the connection at the time, but Herceptin's development-from the discovery of a surface marker on breast cancer cells in 1982 to the U.S. Food and Drug Administration's approval of a drug targeting that marker in September 1998-is a useful study of the financial risks, clinical problems, social ramifications, and rich rewards of personalized medicine.

The defining characteristic of every form of personalized medicine is its biomarker, a kind of biological fingerprint that distinguishes a subset of the patient population. Herceptin is based on a marker protein that sits on the surface of malignant cells. Called neu when it was first discovered by Robert Weinberg's group at MIT in 1982 and more popularly known as Her-2 following its independent isolation in 1985 by Genentech scientist Axel Ullrich, the molecule "listens" for signals that tell a cell to grow and multiply. Large numbers of these receptor molecules turn out to be present in certain aggressive breast cancers because the gene for the receptor is "overexpressed."

As early as 1987 it had become clear that only 25 to 30 percent of women with breast cancer overexpressed the Her-2 gene and might benefit from a drug that blocked the growth signal. But by 1990 scientists at Genentech had developed a drug that would block the Her-2 protein and theoretically would block growth signals to a cancerous cell. "We weren't really thinking of it in terms of individualized medicine back then," says Debu Tripathy, an oncologist at the University of Texas Southwestern Medical Center who participated in the early testing of the drug at the University of California, San Francisco.