IQGAP1 Scaffold-Kinase Interaction Blockade Selectively Targets RAS-MAP Kinase–Driven Tumors

“Upregulation of the ERK1 and ERK2 (ERK1/2) MAP kinase (MAPK) cascade occurs in >30% of cancers1, often through mutational activation of receptor tyrosine kinases or other upstream genes, including KRAS and BRAF2. Efforts to target endogenous MAPKs are challenged by the fact that these kinases are required for viability in mammals34. Additionally, the effectiveness of new inhibitors of mutant BRAF has been diminished by acquired tumor resistance through selection for BRAF-independent mechanisms of ERK1/2 induction…”