Finally, the data presented in this paper may also be placed in the greater context of primary drug resistance given the observation by Straussman et al, that HGF derived from stromal cells results in reactivation of the mitogen-activated protein kinase (a.k.a., Erk1/2) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signaling pathways, in BRAF inhibitor treated cutaneous BRAF mutant melanoma cells [28]. The gene discussed is HGF; the disease is melanoma.