Mechanisms promoting resistances can be manifold: a reactivation of MAPK signaling (amplification or activation of target kinases); bypass via different signaling pathways, e.g., PI3K-Akt-mTOR signaling; or by the surrounding stromal cells, which secrete HGF in BRAFi-resistant melanomas, activating MAPK and PI3K-Akt-mTOR. The gene discussed is AKT1; the disease is melanoma.