Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

Abstract

Background Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional. Methods An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability.Results Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models. Conclusions This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

The Canary in the Coal Mine: The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma

“…16 Patient-derived tumorgrafts have been previously demonstrated to recapitulate the altered pathways of the primary tumor from which they were derived. 17,18 In order to demonstrate similar pathway stability in our cohort and to ensure that any expression differences were not responsible for differences in engraftment, IHC was performed and the correlation between samples was determined. There was excellent inter-rater agreement (K = 0.81–1.00) for IHC scoring between each primary tumor and paired tumorgraft for every marker tested, thus demonstrating expression stability (Table 2).…”

Crizotinib Inhibits Metabolic Inactivation of Gemcitabine in c-Met–driven Pancreatic Carcinoma

“…The engraftment efficiency was about 61% (14), a higher efficiency rate than that we report here for the establishment of primary PDAC cell cultures. However, several studies demonstrated that subcutaneously xenograft models often do not recapitulate the essential features of tumor growth, native tumor microenvironment, and locally invasive and metastatic disease (31), supporting the development of orthotopically implanted tumors as a critical preclinical tool for testing new agents. Another crucial step for the development of the PDAC mouse models consisted of the application of BLI, a low-cost longitudinal in vivo imaging method (32).…”

A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel

“…Luciferase-expressing cells CP15-Luc were established by transducing the parental cells CP15 cell line established from CP15 tumors [33, 34] with a recombinant retrovirus pLHCluc following standard procedures and selected in 0.2 mg/ml hygromycin. Human pancreatic ductal epithelial cells (HPDE) were kindly provided by Dr. FX Real (CNIO, Madrid, Spain).…”