Tuesday, May 29, 2012

Orphan Sleep Drug Findings May Lead To New Cancer Therapies

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Main Category: Cancer / Oncology
Article Date: 26 May 2012 - 0:00 PDT

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'Orphan Sleep Drug Findings May Lead To New Cancer Therapies'


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A new study published in the Proceedings of the National Academy of Sciences reveals that an inexpensive "orphan drug" for the treatment of sleep disorders seems to be a potent inhibitor of cancer cells. Using state-of-the-art technology in a novel approach, the researchers from the Fred Hutchinson Cancer Research Center were able to rapidly analyze the genome, which has far-reaching implications for developing more effective and safer cancer treatments.

Leading researcher Carla Grandori, M.D., Ph.D., an investigator in the Hutchinson Center's Human Biology Division and her team used a high-speed robotic technology (high-throughput screening) together with a siRNA gene silencing, a strong, effective genetic technique to reveal fatal weaknesses in cancer cells that are driven by an oncogene known as "Myc". Oncogenes are generally mutated forms of normal cellular genes that contribute to the production of many cancers, such as brain, breast, lung, liver and ovary cancer.

Until now, scientists believed that Myc was an "undruggable" oncogene that cannot simply be neutralized by the small, stable molecules that would function as a cancer drug. However, even if such drugs would exist, the risk that they would also disable Myc in normal cells and create toxic side effects would be high.

Grandori declared:

"Fortunately, Myc-driven cancer cells have an Achilles heel. Their rapid growth and division damages their DNA, and they rely on other genes to repair that damage. Disabling those genes can cripple the cancer's ability to grow."

Grandori and his team discovered over 100 genes that managed to kill Myc-driven cancer cells without affecting normal cells when blocked, which means that each of these genes could potentially be a target for a new, nontoxic cancer therapy.

One particularly promising gene is CSNK 1 epsilon, which does not just kill cancer without affecting normal tissue when switched off, but it already has an inhibitor for the enzyme it produces, which is a compound that was originally designed to modulate sleep cycles.

Grandori stated: "It had been sitting on a shelf for years, like the thousands of other 'orphan' drugs that are abandoned when they prove ineffective for their intended use."

She purchased the compound online and after developing an appropriate efficacy test, they implanted laboratory mice with Myc-driven neuroblastomas, a deadly cancer of the nervous system that often affects children. Half of the animals were treated with the new compound with the remaining animals being left untreated. The team observed that whilst the untreated mice quickly died of their tumors, those that were treated thrived and their neuroblastomas shrank away.

Grandori, who is also a research associate professor and director of the Quellos High Throughput Screening Core at the University of Washington Department of Pharmacology declared: "It is possible that the next great breakthrough in cancer therapy is already out there, sitting on a shelf, hiding in plain view."

According to Grandori, the combination of high-throughput screening and siRNA silencing could potentially present a radical change to the way in which cancers are treated. She concluded, saying:

"We've barely scratched the surface. These techniques are incredibly powerful, but they're new and not widely known. There are thousands of researchers who could apply this approach to their work. In the right hands, it could speed up the development of new cancer therapies a thousand-fold."

Written By Petra Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our cancer / oncology section for the latest news on this subject. " Functional genomics identifies therapeutic targets for MYC-driven cancer"
Masafumi Toyoshima, Heather L. Howie, Maki Imakura, Ryan M. Walsh, James E. Annis, Aaron N. Chang, Jason Frazier, B. Nelson Chau, Andrey Loboda, Peter S. Linsley, Michele A. Cleary, Julie R. Park, and Carla Grandori
PNAS, May 2012, doi: 10.1073/pnas.1121119109 Please use one of the following formats to cite this article in your essay, paper or report:

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Petra Rattue. "Orphan Sleep Drug Findings May Lead To New Cancer Therapies." Medical News Today. MediLexicon, Intl., 26 May. 2012. Web.
26 May. 2012. <http://www.medicalnewstoday.com/articles/245870.php>


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'Orphan Sleep Drug Findings May Lead To New Cancer Therapies'

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