Major efforts have been undertaken to inhibit constitutive activity of ERK1/2 in cancer,33 but cancer cells are frequently resistant to MEK1/2 inhibitors.34, 35 As we identified a novel TANK-AKT signaling pathway leading to ERK1/2 activation, we tested whether the combined inhibition of MEK1/2 and TBK1/IKKɛ-derived signals could efficiently turn off ERK1/2 activation. The gene discussed is AKT1; the disease is cancer.