Current Progress in Defining New Vulnerabilities in RAS That Can Be Exploited to Therapeutically Inhibit KRAS-Mutant Cancers

Time: 1:00 pm
day: Day Two Track B


  • A new approach to inhibit the oncogenic KRAS by selectively targeting the nucleotide-free (apo) state of the protein
  • Isolation of a monobody termed R15 that selectively binds apo RAS in vitro. When expressed in cells, R15 binds and inhibits oncogenic KRAS mutants with elevated spontaneous nucleotide release rates
  • Contrary to conventional wisdom, it is possible to inhibit oncogenic KRAS by targeting the nucleotide state of the protein. Fidings provide a potential new approach to develop pharmacological inhibitors that target >50% of the oncogenic RAS proteins found in human tumors