Targeting the Tumor Stroma: the Biology and Clinical Development of Pegylated Recombinant Human Hyaluronidase (PEGPH20)

  • Kit Man Wong
  • Kathryn J. Horton
  • Andrew L. Coveler
  • Sunil R. Hingorani
  • William P. Harris
Evolving Therapies (R Bukowski, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Evolving Therapies


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.


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 


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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kit Man Wong
    • 1
    • 2
  • Kathryn J. Horton
    • 3
  • Andrew L. Coveler
    • 1
    • 2
  • Sunil R. Hingorani
    • 1
    • 2
    • 4
  • William P. Harris
    • 1
    • 2
  1. 1.Division of Medical Oncology, Department of MedicineUniversity of Washington School of MedicineSeattleUSA
  2. 2.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  3. 3.Department of MedicineUniversity of Washington Medical CenterSeattleUSA
  4. 4.Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA

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