Combination of rapamycin with trametinib, a MEK1/2 inhibitor, demonstrated strong synergism in HNSCC-derived cells in vitro and in vivo, including HNSCC cells expressing the HRAS and PIK3CA oncogenes….We used UM-SCC-17B, which has a HRAS Q61L mutant and Detroit 562 cells exhibiting the PIK3CA H1047R mutation. The combination of rapamycin and trametinib demonstrated strong synergism in growth inhibition of these cells (Figure (Figure2A,2A, Supplementary Figure S1A).