Finally, Effective Inhibitors of Mutant KRAS

Kirsten rat sarcoma viral oncogene homologue (KRAS) is one of the most highly mutated oncogenes in human cancer, occurring in 95% of pancreatic, 50% of colorectal, and 32% of lung adenocarcinomas and other tumors as well.1 KRAS and two family members, NRAS and HRAS, function as transducers of the signals induced by activated growth factor receptors. RAS is a member of the family of guanine nucleotide–binding proteins. When bound to guanosine diphosphate (GDP), these proteins are inactive. Receptor activation leads to the activation of a family of guanine nucleotide exchange factors (GEFs), which cause GDP to be replaced by guanosine . . .