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Figure 1. Development of acquired gemcitabine resistance in three PDX models of PDAC. Schematic representation of in vivo gemR model development. The schematic shows drug regimen for gemcitabine and times to development of acquired gemcitabine resistance for PA4 (A), PA10 (B), and PA16 (C) PDX models of PDAC. The number (n) of tumors in each cohort is shown in parentheses (A-C); tumor growth curves illustrating changes in sensitivity to gemcitabine in 3 PDX models. Gemcitabine was given once or twice weekly from days 1 through 120-190, as indicated by day of tumor harvest (D-F); tumor growth curves for parental PA4, PA10 and PA16 models (n = 4-5 tumors/cohort) (G). Mice were treated twice weekly with 100 mg/kg gemcitabine or with saline (control) for three weeks. All tumor volumes are reported as mean ± S.E.M. Tumor volumes were compared using two-way analysis of variance (ANOVA) (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). PDAC: pancreatic ductal adenocarcinoma; PDX: patient-derived xenograft