a, KRAS(G12C)-mutant lung cancer cells were treated with the G12Ci alone or in combination with AURKA inhibitor (AURKAi, alisertib, 10 μM) or panAURK inhibitor (tozasertib, 10 μM) to determine the effect on KRAS–GTP levels over time. There is no effect on KRAS–GTP levels with the AURKAi treatment in the absence of the G12Ci treatment. b, RASless mouse embryonic fibroblasts expressing KRAS(G12C) were treated as shown with the indicated concentrations of AURKAi (μM) to determine the effect on KRAS(G12C)–GTP. c, H358 cells stably transfected with doxycycline-inducible AURKA (dox AURKA) were treated with the G12Ci in the presence or absence of doxycycline (2 μg ml−1). Extracts from cells were analysed by immunoblotting to determine the effect on the indicated intermediates. d, H358 doxycycline-inducible AURKA cells were treated as shown and assayed to determine the effect on cell viability (mean + s.e.m, n = 5). A two-tailed t-test P value is shown. e–g, H358 cells stably expressing HA-tagged KRAS G12C under a doxycycline-inducible promoter were treated with doxycycline for 24 h alone (e) or with the indicated inhibitors (f, g). Cell extracts were immunoprecipitated and immunoblotted as indicated. h, KRAS(G12C)-mutant cell lines were treated as shown to determine the effect on cancer cell growth (top) and the presence of treatment synergy (bottom), by using the Bliss index. Red denotes synergy. The mean of three biological replicates is shown on top. i, j, Mice bearing SW1573 (i) or H2122 (j) xenografts were treated with the indicated inhibitors to determine the effect on tumour growth (mean + s.e.m, n = 6 in SW1573, n = 5 in H2122). A two-tailed t-test P value is shown. A representative of at least two independent experiments is shown in a–g. Unless otherwise indicated, n denotes biological replicates. Source data