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Rescuing the guardian of the genome

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Science  07 Oct 2016:
Vol. 354, Issue 6308, pp. 26-28
DOI: 10.1126/science.354.6308.26

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Summary

P53 is a protein that plays a critical role in preventing cells with DNA damage or other cellular insults from turning cancerous. The protein is mutated in about half of all human cancers. When that happens p53 is unable to fold up into its normal 3D shape, which prevents it from latching onto DNA and sounding the cellular alarm in response to damage. Researchers have long tried to combat cancer by boosting the number of copies of healthy p53 in cells, and a number of drugs that do that remain in human trials. But none has yet made it to market. Now, researchers are making headway on a new approach, finding drugs that prop up mutated p53 and restore its proper shape so that it can once again bind DNA and signal for help. One such drug has already passed an initial human trial and others are on the way. If any succeed, they could change the landscape of cancer therapy and perhaps pave the way for other protein-rescuing drugs to combat protein-misfolding diseases such as Alzheimer's and Parkinson's.