RAF1 and non-small cell lung carcinoma: In one study focusing on the treatment of LKB1 wild-type NSCLC cells, it was found that the addition of gefitinib to metformin could inhibit EGFR phosphorylation and its downstream signaling; in addition, increased c-Raf/B-Raf isomerization was found to cause MAPK activation, which induced significant apoptosis in vitro and in vivo (Morgillo et al., 2013).