The aim of the current study was to select cell lines with resistance to MDM2/p53 binding antagonists from cancer cells with druggable targets of the MAPK pathway resulting from either BRAFV600E (WM35) or NRASQ61K (SJSA-1) mutation and to examine whether the MDM2 inhibitor-resistant cell lines retain sensitivity to the MAPK pathway inhibitors, vemurafenib and trametinib. Here, MDM2 is linked to cancer.