THE RAS RENAISSANCE

摘要

When Stephen Fesik left the pharmaceutical industry to launch an academic drug-discovery laboratory, he drew up a wanted list of five of the most important cancer-causing proteins known to science. These proteins drive tumour growth but have proved to be a nightmare for drug developers: they are too smooth, too floppy or otherwise too finicky for drugs to bind to and block. In the parlance ofthe field, they are 'undruggable'. One of the first culprits that Fesik added to his list was a protein family called Ras. For more than 30 years, it has been known that mutations in the genes that encode Ras proteins are among the most powerful cancer drivers. Ras mutations are found in some of the most aggressive and deadly cancers, including up to 25% of lung tumours and about 90% of pancreatic tumours. And for some advanced cancers, tumours with Ras mutations are associated with earlier deaths than tumours without them.