Therapeutics: BRAF; CRAF (RAF1); neuroblastoma Ras viral (v-Ras) oncogene (NRAS); Src

In vitro and mouse studies have identified pan-RAF inhibitors that could help treat drug-resistant melanomas. In vitro, the pan-RAF inhibitors CCT196969 and CCT241161 inhibited multiple Src family kinases - which can drive resistance to BRAF inhibitors in melanoma - with nanomolar potency. In mouse xenograft models of BRAF inhibitor-resistant melanoma, the two pan-RAF inhibitors each caused near complete inhibition of tumor growth compared with the BRAF inhibitor PLX4720 or vehicle. Next steps include Phase I clinical testing...