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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Compliance with Ethical Standards
Conflict of Interest
Kit Man Wong declares that she has no conflict of interest.
Kathryn J. Horton declares that she has no conflict of interest.
Andrew L. Coveler has received institutional funding for the conduct of clinical trials from Halozyme, and has received compensation from Halozyme for serving on an advisory board.
Sunil R. Hingorani has received institutional funding for the conduct of clinical trials from Halozyme, and has received compensation from Halozyme for serving on an advisory board and as a consultant.
William P. Harris has received institutional funding for the conduct of clinical trials from Halozyme, and has received travel support from Halozyme for a scientific presentation at the ESMO annual conference.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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