Innovation Pharmaceuticals Inc (IPIX)

[sox040713]

Another good article on p53.

This protein is mutated in half of all cancers. New drugs aim to fix it before it’s too late

For Amaro and a few other researchers, those computer simulations are an inspiration. "A long-standing dream of cancer biology is to find small molecule drug compounds to restore the activity of p53," Amaro says. "We're very excited about this."

It won't be easy. Restoring normal function to a mutated protein is more difficult than simply blocking a protein, the strategy used by most medical therapies, says Klas Wiman, a tumor cell biologist at the Karolinska Institute in Stockholm. As a result, large drug companies have shied away from the rescue approach and progress has been slow, he says. "It's a little out of the mainstream for big pharma."

The payoff could be big, however. Not only could the strategy treat many kinds of cancer, but just a handful of drugs might be enough, particularly when coupled with chemotherapy drugs that induce the tumor cell damage to which p53 responds. P53 mutations tend to be clustered in the core of the protein, where it binds to DNA, and they have similar effects on its shape. Cell assays and animal studies suggest that drugs that restore p53's activity work with not just one mutant form of the protein, but many, says Alan Fersht, a chemist at the University of Cambridge in the United Kingdom. "The beauty of these things is that they are broadly applicable."

http://www.sciencemag.org/news/2016/10/protein-mutated-half-all-cancers-new-drugs-aim-fix-it-it-s-too-late