MAPK3 and melanoma: It has been demonstrated that MEK variants can contribute to resistant phenotype of melanoma cells, as (i) cells harboring MEK2F57C substitution exerted phospho-MEK2low/phospho-ERK1/2high signature [85], (ii) regrowth of melanoma after initial response to MEK inhibitor has been attributed to MEK1P124L variant [86], and (iii) untreated patients harboring MEK1P124S or MEK1P124L variants faced rapid progression upon administration of BRAF inhibitor [13].