Pancreatic Cancer Xenograft Models

Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer pc.

Pancreatic cancer xenograft models. Genetically engineered mouse models. There is an enormous gap between the antiproliferative and in vivo antitumor efficacy of gemcitabine in cell line based models and its clinical efficacy. Whole genome sequencing of six patient derived xenografts samples demonstrates common mutations and structural variations similar to those reported in primary pancreatic cancer. Aspc 1 capan 1 miapaca 2 bxpc 3 panc 1 xenotransplantation studies have been a backbone of oncology research for four decades and provide an effective research and evaluation environment for novel pharmaceutical compounds.

Multiple recent preclinical studies focus on identifying effective treatments for pdac but the models. This may be due to insensitiveness of the precursor cancer stem cell csc compartment to cytotoxic agents. We sought to establish an in vivo xenograft model that could recapitulate the basal like and classical. The xenograft models were created via the injection of human pdac cell lines into the left and right flank tissues to grow tumors roughly 10 mm in size within 3 4 weeks.

Our pancreatic cancer patient derived xenograft models offer the most translational preclinical model for efficacy screening in cancer drug development. Surgery remains the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma pdac the most common form of pc. Initial attempts to model pancreatic cancer with transgenic mice utilized pancreatic specific gene promoters either the elastase promoter or the rat insulin promoter to drive the expression of oncogenes eg sv40 h ras in acinar and beta cells respectively. However critical aspects of pc responsible for.

The first mouse model of pancreatic cancer that recreates two subtypes of the human. The hedgehog pathway is associated with csc signaling and control. Pancreatic cancer pc is anticipated to be second only to lung cancer as the leading cause of cancer related deaths in the united states by 2030. Derived directly from patient tumors and never adapted to grow in vitro patient derived xenografts reflect the heterogeneity and diversity of the human patient population.

Pdx models are used to create an environment that allows for the natural growth of cancer its monitoring and corresponding treatment evaluations for the original patient. We used a direct xenograft model of pancreatic cancer and a two. Patient derived xenografts pdx are models of cancer where the tissue or cells from a patient s tumor are implanted into an immunodeficient or humanized mouse. For each cell line mice were inoculated with 5 10 6 cells in 200 µl pbs in each flank.

In an effort to develop more reliable preclinical models we have recently established a subcutaneous patient derived xenograft pdx model.