ABSTRACT
Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer. Here, we review various in vitro and in vivo models that are being used or have the potential to be used to study desmoplasia in pancreatic cancer.
Subject(s)
Biomedical Research/methods , Disease Models, Animal , Fibroma/etiology , Pancreatic Neoplasms/physiopathology , Animals , Animals, Genetically Modified , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomedical Research/trends , Cell Line, Tumor , Drugs, Investigational/pharmacology , Drugs, Investigational/therapeutic use , Female , Fibroma/drug therapy , Fibroma/immunology , Fibroma/pathology , Fibrosis , Humans , Male , Mice , Neoplasm Transplantation/methods , Neoplasm Transplantation/trends , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Pancreatic Stellate Cells/drug effects , Pancreatic Stellate Cells/immunology , Pancreatic Stellate Cells/pathology , Pancreatic Stellate Cells/transplantation , Rats , Tumor Cells, Cultured , Xenograft Model Antitumor Assays/methodsABSTRACT
Preclinical research in gynecologic malignancies has largely relied upon cloned cancer-derived cell lines and tumor xenografts derived from these cell lines. Unfortunately, the use of cell lines for translational research has disadvantages because genetic and phenotypic alterations from serial passaging have resulted in expression profiles that are different from the original patient tumors. The patient-derived xenograft (PDX) model derived from human tumor not previously cultured has shown better representation of the heterogeneity of gynecologic malignancies and the human tumor microenvironment with preservation of cytogenetics, cellular complexity, and vascular and stromal tumor architecture. Studies have shown promise with these models to analyze tumor development and adaptation, test drug efficacy, and predict clinical outcomes. Their ultimate value may be seen with preclinical drug screening including novel targeted therapies, biomarker identification, and the development of individualized treatment plans. This article reviews PDX model development, current studies testing chemotherapeutics and targeted therapies, and limitations of the PDX model in gynecologic malignancies.
