Biologists fret over stifling of cancer drugs' development

Medical Matters

Medicine & Science

March 31, 2003|By Judy Foreman | Judy Foreman,SPECIAL TO THE SUN

MOLECULAR biologists aren't generally a grumpy lot, but they are grumbling these days that corporate interests - particularly California-based Geron Corp. - may be stifling development of promising new anti-cancer drugs called telomerase inhibitors.

Telomerase is a weird enzyme - part protein, part RNA. Its job is to restore a tiny bit of DNA at the ends of chromosomes.

As normal cells divide over time, these tiny bits of DNA, called telomeres, get shorter until they virtually disappear. Without telomeres, the cell can no longer divide and dies.

Unlike normal cells, cancer cells keep making telomerase so that telomeres are kept intact. So blocking telomerase with drugs should destroy cancer cells - and indeed it does, at least in the lab.

The grumbling - by some of molecular biology's biggest superstars - involves Geron's ownership and aggressive defense of dozens of telomerase patents. It's unusually bitter because 90 percent of human cancers show overactivity of telomerase, suggesting that they would be vulnerable to anti-telomerase drugs.

At telomere meetings, it's "common for people to sit around and tell Geron horror stories," says Elizabeth Blackburn, professor of biochemistry and biophysics at the University of California, San Francisco School of Medicine.

Blackburn, one of those who discovered telomerase in 1985, once consulted with Geron but no longer has ties to the company.

Carol Greider, the other co-discoverer and a professor of molecular biology and genetics at the Johns Hopkins University School of Medicine, says the legal agreements Geron writes to share materials with others "are often onerous."

Robert Weinberg, a professor of biology at the Massachusetts Institute of Technology, is even more blunt.

"No one in this country has had the temerity to move into this field - they didn't want to risk the litigation," he says. "All this is a shame because telomerase is an extremely attractive target for anti-tumor therapy and Geron, by squatting on its patent estate, has really blocked other people from attempting to develop possible useful anti-tumor drugs."

Geron strenuously disputes this. "Those statements are simply not true," says chief scientific officer Calvin Harley. At a recent meeting in San Francisco and others over the past seven years, he says, "we have shown all our data. We're highly collaborative. We have given our reagents [research materials] to hundreds of labs."

Nobel laureate Tom Cech, president of the Howard Hughes Medical Institute and another telomerase pioneer, undertands that view. "I don't see anything different in the way Geron is treating telomerase than the way any biotech company treats its intellectual property," he says.

Despite the squabbling, telomerase research chugs along. Studies on 20 types of tumors in laboratory dishes and in at least 10 animal models show that blocking telomerase does indeed cause cancer cells to die.

Later this year, Geron expects human trials of a telomere-based drug dubbed GRN163 on patients with a kind of brain cancer called glioblastoma. Geron also is conducting a clinical trial of a telomerase vaccine in 20 men with prostate cancer.

Other ideas are in the pipeline, including tests for telomerase to diagnose cancer from blood samples, making "toxic telomeres" to destroy cancer cells and using viruses controlled by telomerase regulators to kill tumor cells.

All this will take time. But it may also take tinkering with the delicate balance of corporate interests and public health.

Judy Foreman is lecturer on medicine at Harvard Medical School and an affiliated scholar at the Women's Studies Research Center at Brandeis University. Her column appears every other week. Past columns are available on www.myhealthsense.com.

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