RAS proteins play a major, causal role in many human cancers. No therapies have been developed for these cancers because the RAS protein has been considered undruggable given that it has no accessible pocket to which a drug could bind with high affinity, and the mutant proteins that cause cancer are virtually identical to their essential, wild-type counterparts. New technologies in drug development, such as nuclear magnetic resonance–based fragment screening and covalent tethering, and new insights into RAS structure and function have changed this perception and facilitated the development of several drug candidates.


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