Although the first generation of type-II RAF inhibitors (e.g., sorafenib and LY3009120) did not show significant activities in clinical trials, a new generation of pan-RAF inhibitors, e.g., AZ628, TAK632 and LXH254, have been developed and have been demonstrated to reduce phospho-MEK and phospho-ERK levels in the non-BRAFV600 mutant lung cancer H1666 cell line [161], in BRAF mutant human melanoma xenograft models [162,163], and human NSCLC xenograft models [164]. The gene discussed is RAF1; the disease is non-small cell lung carcinoma.