Enzymatic degradation of tumor HA increases tumor perfusion, vascular volume, and extracellular pH, while decreasing tumor hypoxia. A, Tumor HA degradation with low-dose PEGPH20 increased tumor perfusion (left plot), and vascular volume (middle plot), and reduced hypoxia (right plot) in HA-accumulating AsPC-1/HAS3. B, TME pHe increased after treatment with PEGPH20. C, A tabular list of six tumor xenografts and the relative decrease in hypoxia associated with low-dose PEGPH20 treatment.