Intriguingly, Unni et al. showed that synthetic lethality induced by co-expression of mutant KRAS and EGFR is mediated through hyperactivation of ERK in lung adenocarcinoma cells, implying that tumors with mutant oncogenes in the RAS pathway must retain the ERK activity to avoid toxicities that hamper tumor growth [226,227]. The gene discussed is KRAS; the disease is lung adenocarcinoma.