Fig. 6: Targeted MAPK-based combinations require cytotoxic chemotherapy to achieve meaningful therapeutic efficacy.

a Growth kinetics of the indicated PDCL subcutaneous xenograft tumours treated as indicated when the tumours reached 50–100 mm³ in NOD-SCIDγ mice. Dosages of each agent were: ulixertinib 100 mg/kg BID orally 5 days/week, afatinib 12.5 mg/kg orally daily, copanlisib 10 mg/kg by tail vein injection two times/week, gemcitabine 75 mg/kg by intraperitoneal injection once per week. N = 4 tumours per treatment. Data was presented as mean ± SEM. P-values were calculated using one-way ANOVA with Dunnet’s multiple comparisons test. b Clinical and genomic profiles and ERBB2 mRNA expression in PDAC PDX models used in this study. c Waterfall plot summarizing changes of tumour volume from baseline for all 16 PDX models and determination of treatment response using clinical RECIST 1.1. P-values were calculated using Brown-Forsythe and Welch ANOVA test followed by Dunnett’s T3 multiple comparisons test. d Paired data plots showing changes in the body weight of mice treated with different regimens for 4 weeks. P-values were calculated by two-tailed paired t-test. Loss in body weight after two weeks of treatment as indicated. All data are provided in the Source Data file.