Journal
CURRENT ONCOLOGY REPORTS
Volume 19, Issue 7, Pages -Publisher
SPRINGER
DOI: 10.1007/s11912-017-0608-3
Keywords
Pegylated recombinant human hyaluronidase; PEGPH20; Hyaluronic acid; Hyaluronan; Glycosaminoglycan; Pancreatic ductal adenocarcinoma; Interstitial fluid pressure; Stromal resistance; Tumor stroma; Tumor microenvironment; Extracellular matrix; Diffusion; Convection; Tumor perfusion; Gemcitabine; Nab-paclitaxel; Immunotherapy; Thromboembolic events; KPC mice; CD44; RHAMM
Categories
Funding
- Halozyme
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The tumor stroma is increasingly recognized as a key player in tumorigenesis through its effects on cell signaling, immune responses, and access of therapeutic agents. A major component of the extracellular matrix is hyaluronic acid (HA), which raises the interstitial gel fluid pressure within tumors and reduces drug delivery to malignant cells, and has been most extensively studied in pancreatic ductal adenocarcinoma (PDA). Pegylated recombinant human hyaluronidase (PEGPH20) is a novel agent that degrades HA and normalizes IFP to enhance the delivery of cytotoxic agents. It has demonstrated promising preclinical results and early clinical evidence of efficacy in the first-line treatment of metastatic PDA with acceptable tolerability. Moreover, intratumoral HA content appears to be a predictive biomarker of response. Phase 2 and 3 trials of PEGPH20 plus chemotherapy are ongoing in metastatic PDA, and it is also being evaluated in other malignancies and in combination with radiation and immunotherapy.
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