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Genetics Propel New Generation of Cancer Drugs

May 15, 2000|MARLENE CIMONS | TIMES STAFF WRITER

WASHINGTON — Like many scientists who work in the often-frustrating world of cancer research, Dr. Jeff Trent has learned not to show his optimism in public. There have just been too many disappointments.

But Trent, who heads a genetics laboratory at the National Institutes of Health, is excited now--and willing to say so. At a major cancer meeting this week in New Orleans, researchers will unveil the latest results of human experiments that have the field buzzing.

And if recent promising results in human testing are confirmed in subsequent trials, the latest in this new generation of drugs for cancer--tailored to the genetic makeup of individual patients' tumors--could reach the market within two years.

"I think we finally have a window into this field, and I think it's going to work," says Trent, 47, who has done cancer research for more than 20 years. "I'm a believer."

Already, tests using "designer" drugs, which require no horrific chemotherapy, to go after tumor cells while leaving normal cells alone have shown promising results.

When the American Society of Clinical Oncology meets in New Orleans starting Friday, researchers from the Swiss pharmaceutical company Novartis will report the latest data about a group of leukemia patients taking an experimental drug referred to as STI571.

The patients suffer from a blood cell cancer called chronic myelogenous leukemia, a disease in which too many white blood cells are produced. They have been taking a pill once a day that disrupts a cellular signal to the body to produce an enzyme that makes white blood cells proliferate.

In an earlier experiment, 30 of 31 patients taking the drug had returned to a normal white blood cell count within a month of starting treatment. The other patient had a normal white cell count soon after. The promise of the drug has left scientists ebullient.

"Once we understood what it [the enzyme] did to these cells, we had an ideal target," says Elisabeth Buchdunger, a Novartis scientist based in Basel, Switzerland.

The company hopes to file an application for approval with the Food and Drug Administration within a year. If the FDA decides to give the drug fast-track approval, it could be on the market within months after that.

A similar drug, produced by AstraZeneca in Wilmington, Del., also is eliciting interest. Now in expanded human trials, the medicine initially was given to 60 patients with a variety of advanced tumors, among them some of the most difficult to treat, such as one type of lung cancer, esophageal and ovarian cancer.

"We expected the tumors to stop growing, but boy were we surprised: They actually shrunk," says Dr. Gerard Kennealey, the company's vice president for medical oncology.

Although "we don't want the bells to start ringing just yet," he predicts that the drug will have broader application for other cancers, such as colorectal, ovarian, prostate and gastric.

Researchers have known for years that genes in cancer cells perform unique functions that stimulate tumor growth and that finding ways to disrupt this behavior could lead to slowing--perhaps even curing--many kinds of cancer.

Until recently, however, they did not have the tools to identify these genes or to understand their functions. But within the last two or three years, technological advances have brought an explosion of knowledge about how genes work.

Not least among the new tools is microarray, a recently developed computer chip technology that allows researchers to see for the first time how thousands of genes work in concert.

"Instead of looking at a single gene to characterize a cancer, we can look simultaneously at tens of thousands of genes," Trent says. Then, with a sophisticated mathematical analysis of the data, "we can see patterns we couldn't recognize with less data--both within a single cancer and also within a group of cancers."

This technology enables researchers to pinpoint the genetic similarities and differences among patients with the same type of cancer--and, in doing so, helps doctors decide how to treat them.

The National Cancer Institute is so excited about microarray technology that it has awarded $4.1 million to help two dozen cancer research centers in the United States buy microarray equipment.

This is part of a shift in focus at the cancer institute, which is devoting about $650 million in grants annually to molecular medicine. It is redirecting its own drug discovery program to one based on identifying new molecular targets. And it has funded four new centers whose mission is to develop databanks of promising compounds to be screened as cancer agents in custom drugs.

"We are now just starting to see the tip of the iceberg, where the amount of effort that has gone into genetics and into these new tools will lead us to some really big advances, allowing us to individualize treatments based on a tumor's genetic profile," Trent says.

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