In fact, the FDA-approved pan-ERBB inhibitor afatinib (as monotherapy) improved overall survival as shown in genetically engineered mouse models and in patient- and cell line-derived xenografts [140], whereas neratinib (another pan-ERBB inhibitor) proved to be highly efficient only in combination with MEK inhibition in an autochthonous tumor setting [141]. This evidence concerns the gene MAP2K7 and neoplasm.