A Mouse Orthotopic Model Of Pancreatic Cancer And Response To Treatment

The mouse pancreatic ductal adenocarcinoma PAN02 was produced in C57BL/6 mice exposed to 3-methyl-cholanthrene. PAN02 is generally resistant to standard cancer therapeutics, thus providing an appropriately rigorous model for the development of clinically effective agents to treat aggressive and intractable pancreatic ductal adenocarcinoma. Subcutaneous implants of syngeneic PAN02 provide the dual advantages of being able to closely monitor changes in tumor growth without compromising the complex pro- and anti-tumor immune responses of the host that collectively determine the outcome of tumor progression. Unfortunately, subcutaneous PAN02 tends to grow slowly and tumor ulcerations are common which may result in tumor regression or loss of animals in a study. Here we report the growth properties and response to therapy of orthotopically implanted PAN02. To establish the orthotopic model, we implanted cells by direct injection into the pancreas through an incision in the abdominal wall at two implant densities, 3 × 105 and 3 × 106 PAN02 cells in 30 μl. Both cell inocula demonstrated progressive growth with median survival of thirty-seven and thirty days post implant respectively. We chose 3 × 106 PAN02 cells to evaluate efficacy of cytotoxic agents gemcitabine and oxaliplatin. Dosing was initiated 7 days after implant; gemcitabine was dosed at 120 mg/kg, by intraperitoneal injection (IP) every third day for four doses and oxaliplatin was dosed at 10 mg/kg IP once a week for 3 weeks. Gemcitabine and oxaliplatin increased life span by 9.0 days and 20.5 days respectively over vehicle control. The morphology of the tumors revealed by histological staining is also presented. The development of this orthotopic pancreatic model provides a more clinically relevant model for evaluation of novel therapies compared to subcutaneous implantation. Citation Format: Elizabeth Rainbolt, Madelyn Cecil-Taylor, Andrew Wong, Robin Ball, Patrick Wood, Edgar R. Wood, Paula Miliani de Marval, Susan Yeyeodu. A mouse orthotopic model of pancreatic cancer and response to treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2760.