July 2001

DNA Chips Target Cancer

Within a few years, DNA microarrays could help diagnose and treat this killer, perhaps even before tumors form.

By Marc Wortman

In preparation for minor surgery, John Leventhal needed a routine chest x-ray.When the New Haven, CT, doctor joined the radiologist who was examining the film, he was shocked by what he saw: an opaque blotch deep in his lung. "As a physician," says Leventhal, "you're taught in medical school that when you see a mass like that, it means lung cancer." Leventhal's medical training also taught him that to confirm the diagnosis, his doctors would need to crack open his rib cage to get a piece of the suspect tissue that would be closely examined by a pathologist-an extremely painful and hazardous operation. The weekend before that surgery, Leventhal went off on a family ski vacation. He recalls thinking, "This is the last time I will go skiing for a long, long time."

That was five years ago. Today the medical profession's way of dealing with cancer could be about to change. Around the same time that Leventhal underwent
surgery, researchers at Stanford University and Santa Clara, CA-based startup Affymetrix were beginning to build the first "DNA microarrays."More commonly known as DNA chips, these are DNAcovered silicon, glass or plastic wafers capable of analyzing thousands of genes at a time to, for example, identify the ones that are active in a sample of cells. Now these microarrays appear poised to join the war on cancer. DNA chips, predicts National Cancer Institute director Richard Klausner, are "going to have a huge effect" on the diagnosis and treatment of the disease.

One reason for the excitement is that DNA chips offer a whole new-and potentially much earlier, easier and more precise-way of detecting cancerous cells. Most forms of cancers go unnoticed until lumps, coughs or pains develop, at which point it is often too late. And even then, once a pathologist gets a biopsy from a tumor, distinguishing one form of cancer from another can be difficult or even impossible with existing techniques, which involve noting distortions in the cells' architecture under a microscope. Better diagnostic information could be used to make better treatment decisions, perhaps making the difference between life and death.

ithin the next two years, pathologists expect to begin using DNA-chip-based tools to spot genetic differences among cells; these telltale differences could be used to help detect cancerous cells long before symptoms develop and to distinguish one type of cancer from another. In short, the chips will provide a genetic profile of a cancerous cell that can be read like a criminal's rap sheet. The physician will know where the cancerous cell originated, how far it has progressed, and which therapies will work best to halt its further growth and spread.

Leventhal was lucky. His lung biopsy was negative, and he was back on the slopes the next winter. But it took him a month to recover from the biopsy surgery, and today he has an angry scar down the middle of his chest to remind him of the ordeal. By the end of the decade, it is likely that a patient like Leventhal will be able to skip invasive diagnostic procedures altogether. A DNA-chip-based device might be able to read a sputum sample right in the doctor's office, checking for the genetic changes in the lung cells that are naturally sloughed off into the viscous fluid. If the news is bad, the patient might well have a host of new treatment options. That's because DNA chips are also speeding the discovery of new and better cancer drugs. "We're on the threshold of a new era," says Klausner. "Technologies like DNA chips will tell us not only that something may be amiss, but what it is and what we can do about it."