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Breakthrough: One Drug Targets Many Cancers

January 5, 2010
In two preclinical studies, an experimental drug currently being tested against breast and lung cancer shows promise in fighting the brain cancer glioblastoma (the most common malignant brain tumors in adults) and prostate cancer, say researchers at UT Southwestern Medical Center. The drug's actions are especially encouraging because they attacked not only the bulk of the tumor cells, but also the rare cancer stem cells believed to be responsible for most of a cancer's growth, said Dr. Jerry Shay, professor of cell biology and a senior co-author of both papers. In the glioblastoma study, which appears in the January issue of Clinical Cancer Research, the drug also crossed from the bloodstream into the brain, which is especially important because many drugs are not able to cross the blood-brain barrier, making glioblastomas particularly difficult to treat with drugs. "Because it attacks a mechanism that's active in most cancers, it might prove to be widely useful, especially when combined with other therapies," said Dr. Shay. He and his colleagues study telomeres, bits of DNA that help control how many times a cell divides. Telomeres are protective "caps" of DNA on the ends of chromosomes, the structures that contain the body's genes. As long as telomeres are longer than a certain minimum length, a cell can keep dividing. But telomeres shorten with each cell division, so a cell stops dividing once the telomeres are whittled down to that minimum. In cancer cells, however, an enzyme called telomerase keeps rebuilding the telomeres, so the cell never receives the cue to stop dividing. In essence, they become immortal, dividing endlessly. Imetelstat, the drug used in these studies, blocks telomerase. The research focused on cells called tumor-initiating cells. Some believe that tumors contain a small subset of initiating cells–or cancer stem cells–able to initiate and drive tumors and are often resistant to radiation therapy and chemotherapy. In the glioblastoma study, Dr. Shay and his colleagues found that imetelstat blocked the action of telomerase in isolated tumor-initiating cells as well as the bulk of the tumor cells, eventually killing them. Combining imetelstat with radiation and a standard chemotherapy drug made imetelstat even more effective. When the researchers implanted human tumor-initiating cells into rodents, they found that imetelstat was able to enter brain tissue and inhibit telomerase activity. In the prostate cancer study, available online in the International Journal of Cancer, the researchers isolated tumor-initiating cells from human prostate cancer cells. The cells showed significant telomerase activity. Imetelstat blocked the enzyme's activity, and telomeres shortened greatly.