For instance, the use of the next-generation type 1.5 (αC-helix OUT) RAF inhibitor PLX8394, which abolishes the paradoxical ERK activation “paradox-breaker”, prevented the BRAF inhibitor monotherapy-mediated drug resistance in BRAFV600E-mutant NSCLC [137]. Here, MAPK1 is linked to non-small cell lung carcinoma.