However, efficacy could be limited because of drug resistance.277,278 While exploring the mechanism of BRAF inhibitor resistance in melanoma, researchers found that the upregulation of MOB3B and activation of the Hippo pathway contribute to vemurafenib resistance.279 In addition, NF2 is involved in vemurafenib resistance.280 Regarding MEK inhibitor resistance, the Hippo pathway may play an essential role. This evidence concerns the gene BRAF and melanoma.