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Experimental Breast, Lung Cancer Drug Shows Promise


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US researchers have completed two preclinical studies, one on isolated human cells and the other on rodents, that concluded an experimental breast and lung cancer drug shows promise against prostate cancer, and glioblastoma, a type of brain cancer.

Both studies were done by researchers at the University of Texas (UT) Southwestern Medical Center in Dallas; the glioblastoma study appears in the January issue of Clinical Cancer Research, and the prostate cancer study is available online in the International Journal of Cancer.

The senior co-author of both papers is Dr Jerry Shay, professor of cell biology at UT Southwestern. He told the media that the findings are especially encouraging because the drug appeared to attack not only the bulk of tumor cells but also the rare cancer stem cells that many scientists believe drive the growth of a cancer.

"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 Shay.

According to the American Cancer Society, glioblastomas are the most common malignant brain tumors in adults; however they are difficult to treat because most drugs can't pass through the blood-brain barrier: the blood vessels in the brain have very tight walls that only allow few substances to get through.

However, in the glioblastoma study, which was done on mice, Shay and colleagues showed that the drug also went through the blood-brain barrier.

Shay and his team specialize in investigating telomeres; the protective caps of DNA on the ends of chromosomes, the structures that encapsulate our genes. These bits of DNA control how many times a cell divides, and in normal cells they get shorter each time division takes place.

Cells keep dividing until the telomeres shorten to within a minimum length: after that, they don't divide any more.

But, in cancer, this mechanism breaks down, because an enzyme called telomerase keeps rebuilding the telomeres, so the cells (or rather their descendants) never stop dividing, thus fuelling uncontrolled growth.

The experimental drug at the centre of these studies is called imetelstat or GRN163L and is made by Geron Corporation, who provided the drug for both studies.

Imetelstat blocks the action of the telomerase enzyme and is already being tested in clinical trials for use against breast cancer, lung cancer and chronic lymphocytic leukemia.

For the two studies, Shay and colleagues focused on cancer stem cells: a small subset of of initiating cells that kick off and drive the growth of tumors, so some researchers believe. These cells are also quite tough: they tend to resist radiation and chemotherapy.

In the brain cancer study, the researchers found that the drug blocked telomerase in isolated tumor-initiating cells and it also blocked the enzyme in the bulk of the tumor cells, eventually killing them.

When they combined the drug with radiation and chemotherapy, the effect was even greater. And when they implanted mice with human tumor-initiating cells, they showed that the drug went into brain tissue and blocked telomerase activity there as well.

In the prostate cancer study, which was published online last November, Shay and colleagues isolated tumor-initiating cells from human prostate cancer cells and showed that the drug blocked their telomerase activity, resulting in significant shortening of telomeres.

The glioblastoma study was sponsored by the National Institutes of Health, and the prostate cancer study was supported by a Department of Defense Prostate Cancer Training Award and the Southland Financial Corporation.

"The Telomerase Antagonist, Imetelstat, Efficiently Targets Glioblastoma Tumor-Initiating Cells Leading to Decreased Proliferation and Tumor Growth."

Calin O. Marian, Steve K. Cho, Brian M. Mcellin, Elizabeth A. Maher, Kimmo J. Hatanpaa, Christopher J. Madden, Bruce E. Mickey, Woodring E. Wright, Jerry W. Shay and Robert M. Bachoo.

Clin Cancer Res January 1, 2010 16:154-163

Published Online First January 4, 2010


"The effects of telomerase inhibition on Prostate tumor-initiating cells."

Calin O. Marian, Woodring E. Wright, Jerry W. Shay

International Journal of Cancer, Volume 9999 Issue 999A, Page NA, Published Online: 11 Nov 2009.


Source: UT Southwestern.

Written by: Catharine Paddock, PhD

Copyright: Medical News Today

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