PTPN11 and neoplasm: Moreover, the administration of trametinib in combination with IACS-13909 resulted in an approximately 82% reduction in tumor size (Figure 6E and Supplemental Figure 6B), thus confirming the effectiveness of MEK1/2/SHP2/autophagy triple inhibition in resensitizing RAS-MAPK–driven cancer cells that become otherwise insensitive to RAS-MAPK inhibition.