Furthermore, it has to be taken into account that BRAF-mutant melanomas may acquire BRAF inhibitor resistance via up-regulation of both MAPK and PI3K/Akt pathways in about 22% of the melanoma patients [49], whereas other drugs targeting different cellular pathways may escape development of drug resistance, probably due to the extraordinary plasticity of melanoma cells [56,57,58]. The gene discussed is BRAF; the disease is melanoma.