Fig. 3

Degradation of hyaluronic acid renders chemoresistant tumors sensitive to anticancer drugs by attenuating the collapse of blood vessels. The stroma associated with pancreatic ductal adenocarcinoma (PDAC) shows a robust and complex desmoplasia, with notable hyaluronic acid (HA) content and the collapse of blood vessels in response to high interstitial fluid pressure (IFP). Stromal stiffness is positively correlated with the Hippo pathway. PEGPH20 contributes to the enzymic degradation of HA and decreases the degree of stromal stiffness [102]. The attenuated IFP broadens the lumen of tumor vessels, thereby increasing the efficacy of drug delivery. A clinical trial of PEGPH20 in advanced solid tumors is ongoing [107]