In an attempt to further optimize the therapeutic potential of trametinib, vertical double targeting of the RAF-MEK-ERK cascade, using RAF1 Proto-Oncogene, Serine/Threonine Kinase (RAF1) or pan-RAF inhibitors combined with MEK/ERK inhibitors, synergistically triggered myogenic differentiation and suppressed embryonal RMS tumor growth [188]. Here, RAF1 is linked to neoplasm.