Targeting Adaptive Resistance to RAS/MAPK-Directed Therapies

Time: 12:25 pm
day: Day One


  • Adaptive resistance and RAS/MAPK reactivation limits therapeutic response to RAS/MAPK targeting agents
  • Development of inhibitors targeting components of the RAS/MAPK adaptive machinery (inhibitors of RTKs, SHP2, SOS, dimeric RAF) enables the development of more effective combinatorial therapeutic approaches
  • Effective targeting of components of RAS/MAPK in their native conformations in cells requires elucidating and exploiting allosteric properties of inhibitors
  • We propose mechanism-based combinatorial strategies for potent RAS/MAPK inhibition in the tumor while retaining a high therapeutic index