Furthermore, the combination of the BRAF and MEK inhibitor results in an increase in HDAC8 expression in melanoma cells and this increase leads to the regulation of MAPK and AP-1 signaling cascades through EGFR and proto-oncogene MET, which contributes resistance to the BRAF and MEK inhibitors and melanoma cells expressing HDAC8 observed resistance to the BRAF inhibitor treatment with nuclear translocation of c-Jun. The gene discussed is MAP2K7; the disease is melanoma.