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Researchers Identify Potential New Drug for Inherited Cancer

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Key Points

  • Neurofibromatosis type 2 is an inherited cancer that leads to tumors of the auditory nerve that connects the inner ear to the brain.
  • FRAX97 was found to slow down progression of neurofibromatosis type 2 in animal models and reduces more than 80% of PAK1 activity.

Scientists from The Scripps Research Institute have identified a new drug candidate for an inherited form of cancer with no known cure. The new study showed the drug candidate—known as FRAX97—slowed the proliferation and progression of tumor cells in animal models of neurofibromatosis type 2. This inherited type of cancer, caused by mutations in the antitumor gene NF2, leads to tumors of the auditory nerve that connects the inner ear to the brain.

The new compound, originally developed to treat neurodegenerative disease, targets a protein family known as p21-activated kinases or PAKs. These kinases play a critical role in the development of neurofibromatosis type 2. PAK1 has also been implicated in the growth of breast and lung cancers.

“Our study shows that if we inhibit these kinases we can counter the formation of tumors in this brain disease,” said lead author Joseph Kissil, PhD, Associate Professor at The Scripps Research Institute.

Study Details

In the new study, published in the October 4, 2013 issue of The Journal of Biological Chemistry, Dr. Kissil and colleagues showed that the inhibitor slows down progression of neurofibromatosis type 2 in animal models and reduces more than 80% of PAK1 activity.

Dr. Kissil noted that a key challenge in developing drug candidates is finding potential agents that are both potent and highly selective for their targets—limiting its action to the desired arena and reducing unwanted side effects.

“This inhibitor turned out to be both potent and highly selective,” he said. “The real question is why. We were able to show that it works through a unique mechanism.”

While the binding site on PAK1 is quite large, it also contains a smaller pocket that juts off the larger site. The inhibitor not only takes up space in the larger site, but enters the back pocket as well. That extra binding gives the inhibitor its strong selectivity.

The study was supported by the National Institutes of Health, the American Cancer Society, and Afraxis, Inc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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