New drug for inherited cancer identified

 Scientists have identified a new drug that can potentially treat an inherited form of cancer that has no cure.

 The new study showed the drug candidate - known as FRAX97 - slowed the proliferation and progression of tumour cells in animal models of Neurofibromatosis type 2.

This inherited type of cancer, caused by mutations in the anti-tumour gene NF2, leads to tumours of the auditory nerve that connects the inner ear to the brain.

 The new compound, originally developed to treat neuro-degenerative disease, targets a protein family known as p21-activated kinases or PAKs.

 These kinases (enzymes that add a phosphate group to other proteins and change their function) 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 tumours in this brain disease," said an  associate professor who led the study.

 In the new study, researchers showed that the inhibitor slows down progression of Neurofibromatosis type 2 in animal models and reduces more than 80 per cent of PAK1 activity.

They noted 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," he said.

 While the binding site on PAK1 is quite large, it also contains a smaller pocket, a kind of back-room 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.

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