Fig. 6: MEK5/ERK5 inhibition synergizes with standard of care treatments.

a H460 scramble cells and H460 ERK5 CRISPR clones (#20 and #57) were plated in 24-well dishes, and 24 h later treated with the indicated doses of standard of care agents for 48 h. Cell viability was measured by an MTT assay and each condition (scramble, #20 and #57) was represented as percentage from their respective untreated cells. Results are expressed as mean ± SD of an experiment that was repeated twice. Error bars are shown. The IC50 values and p-values for each drug and condition are also indicated (***p ≤ 0.001). b In vivo analyses of the effect of BIX02189 and JWG-071 (c) alone or in combination with standard of care drugs, on the growth of H460 cells subcutaneously implanted in mice and treated with the indicated drugs as described under the “Methods” section. Tumor masses (n = 8–10 tumors per group) were measured daily for two weeks. The mean tumor volume and SEM error bars of each group are represented. To avoid excessive overlapping of the curves, the data of the drug combination with BIX02189 or JWG-071 were split in (b, c). Therefore, please notice that the curves for control, pemetrexed, crizotinib or cisplatin are the same in both (b, c). Exact p-values of comparisons between control untreated and treated groups are shown in Supplementary Table 1e and g.