10/2/2005

The Palm Beach Post

By Jeff Nesmith

Washington -- After Nancy was diagnosed with breast cancer in 2002, she had a mastectomy, radiation and chemotherapy. Six months later it appeared that her tumors were eliminated.

"All my blood work and scans have been A-OK since then," she said two months ago in a message she left on an Internet breast cancer support forum. Like other participants, she signed her message with her first name only.

But last May, efforts to deal with complications from gallbladder surgery caused her shocked surgeons to discover that her lungs were "riddled" with cancer, she said. The tests and scans had been wrong.

"Tests came back that it was BC," Nancy, 43, told the other breast cancer victims who exchange experiences, sympathy and encouragement on the computer forum, "and since then we have found out it is in a bunch of places in my bones."

"Just wanted to say hi," she wrote. "I never thought things would get so bad so quickly. . . . I am absolutely scared to death."

Nancy is among 25 percent of breast cancer patients whose suffering and fear appear in large part due to the aberrant behavior of a protein that scientists know as "Human Epidermal Growth Factor Receptor 2," or just Her2.

One of several hundred thousand different proteins in the human body, Her2 normally sits quietly in the membrane of a cell until another molecule latches onto it and turns it on. Once activated, Her2 turns on other proteins involved in controlling the way the cell functions.

For reasons not fully understood, Her2 sometimes runs amok, multiplying enormously. In scientific terms, the protein is "over-expressed."

When that happens, Her2 abandons its role in regulating a normal cellular activity and triggers a rampage of chemistry, leading to proliferation of breast cancer, as well as some other cancers.

Drugs such as Taxol and Herceptin have been used by oncologists to suppress the growth of tumors and at least temporarily cause them to shrink. Success has been modest and varied.

In the hope of one day finding more drugs for cancer and other diseases, the National Institutes of Health has set out on a new approach to understanding proteins and controlling their behavior.

Several hundred thousand different kinds of proteins in the human body control countless chemical actions within and between cells. They determine whether we produce antibodies to influenza virus, whether we develop or resist cancer, whether our thoughts are clear and lucid or lead us into the scrambled confusion of schizophrenia. They cause lightning bugs to glow and help earthworms find mates in the darkness of dirt.

Working with collaborating scientists at Emory University and eight other research centers, NIH hopes to open a new avenue for studying proteins.

Raymond Dingledine, chairman of the department of pharmacology at the Emory University School of Medicine, explained that proteins are much more than tiny lumps of "stuff." Each is intricately designed by nature for a specific function.

When another protein or a small molecule attaches itself to an irregular spot on the protein's surface, the protein may wiggle or reshape itself, excite other proteins or shut down completely.

NIH officials hope the small molecules will be like a set of keys that turn the gadgets on and off. With such a key in hand, a scientist can block a particular protein in a tissue culture or a laboratory animal and learn a lot about the protein's normal activity.