title: Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer.
abstract: Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic agents. We discuss the genesis and consequences of altered fluid dynamics in PDA and strategies to restore them.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Provenzano
authors.forename: S R
authors.initials: SR
authors.lastname: Hingorani
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000503:physiopathology*; D019008:Drug Resistance, Neoplasm; D045604:Extracellular Fluid / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D057446:Hydrodynamics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D006820:Hyaluronic Acid