Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer.

OBJECTIVEPancreatic ductal adenocarcinoma (PDA) is characterised by stromal desmoplasia and vascular dysfunction, which critically impair drug supply. This research examines the function of an plentiful extracellular matrix element, the megadalton glycosaminoglycan hyaluronan (HA), as a novel therapeutic goal in PDA.METHODSUsing a genetically engineered mouse mannequin of PDA, the authors enzymatically depleted HA by a clinically formulated PEGylated human recombinant PH20 hyaluronidase (PEGPH20) and examined tumour perfusion, vascular permeability and drug supply. The preclinical utility of PEGPH20 together with gemcitabine […]