title: The role of pancreatic stellate cells in pancreatic cancer.
abstract: Since conventional and targeted therapies aiming at cancer cells have largely failed to prolong survival in pancreatic cancer, targeting the infrastructure of the tumor, hence its stroma is a novel strategy. It is believed that fibrotic and hypovascular stroma forms a barrier around cancer cells, hindering effective delivery of chemotherapy. Theoretically, antifibrotic therapy should reduce the compactness of the stroma and reduce the interstitial pressure, allowing better delivery of chemotherapy. This approach has worked successfully in a genetically engineered mouse model but failed in humans, paradoxically increasing mortality in the treatment arm. Normally, stromal cells deposit extracellular matrix as an innate defensive reaction to form a barrier between what is harmful and the rest of the body. Despite the significant amount of in vitro data suggesting the pro-tumorigenic roles of activated stellate cells, there is no reason to believe that stellate cells around genetically mutated cells are from the beginning there to support carcinogenesis. Such a stromal activation is also observed around PanIN lesions (which harbor genetically mutated cells) in chronic pancreatitis, where no cancer develops. In pancreatic cancer, the selection pressure created by the fibrotic and hypoxic stroma eventually leads to the evolution of more aggressive clones, indirectly contributing to the aggressiveness of the tumor. Here, the main problem is the late diagnosis of pancreatic cancer, which gives cancer cells enough time for malignant evolution. Therefore, applying antifibrotic therapy at a late stage can be counterproductive. It may increase delivery of chemotherapy, but also lead to the escape of cancer cells.
authors.affiliation: Department of General Surgery, Technische Universität München, Klinikum rechts der Isar, 81675 Munich, Germany. m.mert.erkan@googlemail.com
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic; D005355:Fibrosis / Q000188:drug therapy; D015972:Gene Expression Regulation, Neoplastic; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D010179:Pancreas / Q000166:cytology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents