Platform of Orthotopic Models Suitable for Preclinical Validation of Therapies in Human Pancreatic Cancer
R Miquel, S Perez-Torras, A Vidal-Pla, V Almendro, L Fernandez-Cruz, S Navarro, J Maurel, N Carbo, P Gascon, A Mazo. Hospital Clinic, IDIBAPS, Barcelona, Spain; School of Biology, UB, Barcelona, Spain
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high dissemination at early stages together with a bad response to both radio- and chemotherapy. Efforts to find new therapies for human pancreatic ductal adenocarcinoma have not resulted in clear improvements on patient survival. Prognosis is still very poor with a 5 year-median survival of 1-4% and a median survival period after diagnosis of only 4-6 months. Although a great deal of efforts has been carried out until now, there is still an urgent need to develop new therapies to improve the prognosis of these patients.
Design: This situation has prompted us to generate an in vivo platform of human orthotopic PDAC models by direct implantation of fresh surgical material from human tumor tissue into the pancreas of athymic mice. Tissue microarrays from the primary human tumors and from the xenografted tumors and their consecutive passages were performed. Histological features, immunohistochemical expression of different markers and protein expression and gene status of several tumor supressor genes and EGFR family were compared.
Results: A total of eleven orthotopic xenografts were obtained. Models show stable growth kinetics and representative metastatic behavior. We found a high degree of histological and molecular similarities between patient tumors and the xenografts. Tissue-microarrays studies demonstrate preservation and maintenance of protein expression patterns through passages.
Conclusions: The orthotopic approach we present as a platform established directly from 11 patients offers a good possibility to progress in pancreatic cancer knowledge and treatment. They constitute a useful and worthy preclinical model for further exploring the biological basis of human pancreatic cancer and to draw from them more accurate therapeutic responses with clinical significance.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 213, Tuesday Afternoon