Blocking Enzyme Could Help Cancer
Randolph E. Schmid,
Associated Press Writer

2:00 AM EST; September 28, 1999; Washington, D.C. (AP) -- In an experiment that could point the way to a new approach to fighting cancer, scientists blocked the enzyme that most forms of cancer need to continue growing. Working with laboratory cell cultures, researchers prevented cancer cells from producing the enzyme telomerase. That caused the cells to stop their reproduction and die. "We haven't developed a ... therapeutic drug," stressed Dr. Robert Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, a member of the research group. He said the method used in the laboratory study is not practical in humans. But, Weinberg said, the findings being published in the October issue of the journal Nature Medicine point the way for pharmaceutical companies to search for drugs that do the same thing.

Dr. Jerry Shay of the University of Texas Southwestern Medical Center called the report "very dramatic proof of the principle that inhibiting telomerase may in fact lead to the death of cancer cells." Shay, a leading cancer researcher, was not a member of Weinberg's research team. In normal human cells, structures called telomeres protect the ends of the DNA that codes the cell's purpose. Each time the cell reproduces, the telomeres shrink slightly, until they reach a critical length that stops the cell from reproducing and it dies. Scientists have learned that 80 percent to 90 percent of cancer cells have developed the ability to produce the enzyme telomerase, which protects the telomeres, allowing the cell to keep reproducing indefinitely, growing into a tumor. These cells produce a chemical called hTERT that provides a template for the creation of telomerase.

Weinberg and his fellow researchers altered hTERT into a negative form that blocks telomerase production. In laboratory experiments, they inserted the so-called negative-hTERT into human colon, ovarian, and two types of breast cancers. With the negative-hTERT present, the cells stopped producing telomerase, their telomeres began to shrink with each mitotic division, and the cells eventually stopped reproducing and died. When they injected mice with the treated cells, tumors failed to develop. Mice injected with untreated versions of the same cells developed cancer.

Weinberg's team used a form of gene therapy to introduce the negative-hTERT into the cancer cells. "That is practicable in a culture dish, but it isn't practicable in a living animal bearing a tumor," he said. "That's why it's not convertible to therapeutic potential. I really believe over the next several years one company or another will develop a chemical to interfere with this enzyme," he added. "But one has to be very clear and explicit that such a chemical does not yet exist."

Weinberg added that if a telomerase-interfering drug were developed, it would need to be used in conjunction with other therapy because it does not always act quickly. In the colon cancer cells, which have short telomeres to begin with, reproduction stopped promptly. But the breast cancer cells continued to proliferate for 10 to 20 days before stopping and the ovarian cancer cells took 30 to 40 days to be affected. In many cases, he said, it would be useful to remove the bulk of the cancer first and then use anti-telomerase therapy to clean out small remaining nests of the disease. Besides Weinberg, the research team included scientists from the Massachusetts Institute of Technology, the Dana-Farber Cancer Center, Brigham and Women's Hospital and Harvard Medical School.