Abstract 812: Multiplatform modeling of pancreatic cancer using patient-derived cells: A new approach for defining drug resistance mechanisms

作者：Erika Parasido, Praathibha Sripadhan, George Avetian, Richard Schlegel, Jonathan R. Brody, Jordan M. Winter, Charles J. Yeo, Michael J. Pishvaian, Erik Glasgow, Stephen W. Byers, Christopher Albanese · 发表于：Cancer Research · 年份：2017 · DOI：10.1158/1538-7445.am2017-812 · 研究领域：3D Printing in Biomedical Research、Cancer Cells and Metastasis、Pancreatic and Hepatic Oncology Research

Abstract Background: Pancreatic adenocarcinoma (PA) is the fourth leading cause of cancer-related death in the USA. Current treatments utilize Gemcitabine alone or in combination with other drugs, such as nab-paclitaxel, however, a growing number of patients have shown resistance to these regimes. In order to enhance clinical response, it is important to better understand the mechanisms of drug resistance. To date, one of the main limitations in PA research has been the reliance on a few commercially available PA cell lines or a limited number of genetically engineered or PDX mouse models for in vitro and in vivo studies. It was therefore imperative to develop more accurate cellular models that better represent a given patient’s tumor. In our current study, we present the use of patient-derived primary PA cells as a model system for basic and translational research, and for personalized medicine. Methods: Patients’ biopsies were collected after surgery, and long-term cultures of PA cells were established using the conditional reprogramming of cells (CRC) approach we developed. KRAS and p53 sequencing verified the PA origin of both the patient samples and the matched CRC lines. The IC50s for Gemcitabine and Abraxane were determined and used to establish drug resistant clones. Our two dimensional (2D) CRC cultures have shown to be adaptable to different platforms, such as 3D spheroid cultures as well as zebrafish- and mouse- PDX models. Results: We established KRAS-mutant prima...