In HRAS- or NRAS-mutated cells, neither SHP2 or SOS1 inhibitors are effective as single agents [133,135,138], however, a recent study showed that while NRASQ61-mutated neuroblastoma cells were insensitive to SHP2 inhibitors alone, combined SHP2 and MEK inhibition showed synergistic inhibition of cell growth [138], suggesting that proximal RTK (SHP2 or SOS1) inhibitors may be a general therapeutic option to overcome MEK inhibitor resistance in RAS-mutated cancer cells. The gene discussed is SOS1; the disease is neuroblastoma.