title: Stromal biology and therapy in pancreatic cancer: a changing paradigm.
abstract: Pancreatic ductal adenocarcinoma (PDA) exhibits one of the poorest prognosis of all solid tumours and poses an unsolved problem in cancer medicine. Despite the recent success of two combination chemotherapies for palliative patients, the modest survival benefits are often traded against significant side effects and a compromised quality of life. Although the molecular events underlying the initiation and progression of PDA have been intensively studied and are increasingly understood, the reasons for the poor therapeutic response are hardly apprehended. One leading hypothesis over the last few years has been that the pronounced tumour microenvironment in PDA not only promotes carcinogenesis and tumour progression but also mediates therapeutic resistance. To this end, targeting of various stromal components and pathways was considered a promising strategy to biochemically and biophysically enhance therapeutic response. However, none of the efforts have yet led to efficacious and approved therapies in patients. Additionally, recent data have shown that tumour-associated fibroblasts may restrain rather than promote tumour growth, reinforcing the need to critically revisit the complexity and complicity of the tumour-stroma with translational implications for future therapy and clinical trial design.
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Centre Goettingen, Georg August University Goettingen, Goettingen, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Neesse
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hana
authors.initials: H
authors.lastname: Algül
authors.affiliation: Cold Spring Harbor Laboratory, Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
authors.affiliation: Department of Gastroenterology, Endocrinology, Infectiology and Metabolism, Philipps-University, Marburg, Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gress
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001707:Biopsy, Needle; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D005544:Forecasting; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D011379:Prognosis; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents
keywords: PANCREATIC DISEASE; PANCREATIC FIBROSIS; PANCREATIC PATHOLOGY; PANCREATIC TUMOURS; PANCREATITIS