Activating mutations in some isoforms of Ras or Raf are drivers of a substantial proportion of cancers. The main Raf effector, Mek1/2, can be targeted with several highly specific inhibitors. The clinical activity of these inhibitors seems to be mixed, showing efficacy against mutant BRAF-driven tumors but not K-Ras-driven tumors, such as pancreatic adenocarcinomas.
To improve our understanding of this context-dependent efficacy, we generated pancreatic cancer cells resistant to Mek1/2 inhibition, which were also resistant to KRAS and Erk1/2 inhibitors. Read more . . .