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

doi:10.1007/s11912-017-0608-3

Review

. 2017 Jul;19(7):47.

doi: 10.1007/s11912-017-0608-3.

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

Kit Man Wong^{1

2}, Kathryn J Horton³, Andrew L Coveler^{1

2}, Sunil R Hingorani^{1

2

4}, William P Harris^{5

6}

Affiliations

¹ Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
² Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³ Department of Medicine, University of Washington Medical Center, 1959 NE Pacific Street, Box 354760, Seattle, WA, USA.
⁴ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M5-C800, Seattle, WA, 98109-1024, USA.
⁵ Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. wph3@u.washington.edu.
⁶ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. wph3@u.washington.edu.

PMID: 28589527
DOI: 10.1007/s11912-017-0608-3

Review

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

Kit Man Wong et al. Curr Oncol Rep. 2017 Jul.

. 2017 Jul;19(7):47.

doi: 10.1007/s11912-017-0608-3.

Authors

Kit Man Wong^{1

2}, Kathryn J Horton³, Andrew L Coveler^{1

2}, Sunil R Hingorani^{1

2

4}, William P Harris^{5

6}

Affiliations

¹ Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
² Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³ Department of Medicine, University of Washington Medical Center, 1959 NE Pacific Street, Box 354760, Seattle, WA, USA.
⁴ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M5-C800, Seattle, WA, 98109-1024, USA.
⁵ Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. wph3@u.washington.edu.
⁶ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. wph3@u.washington.edu.

PMID: 28589527
DOI: 10.1007/s11912-017-0608-3

Abstract

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.

Keywords: CD44; Convection; Diffusion; Extracellular matrix; Gemcitabine; Glycosaminoglycan; Hyaluronan; Hyaluronic acid; Immunotherapy; Interstitial fluid pressure; KPC mice; Nab-paclitaxel; PEGPH20; Pancreatic ductal adenocarcinoma; Pegylated recombinant human hyaluronidase; RHAMM; Stromal resistance; Thromboembolic events; Tumor microenvironment; Tumor perfusion; Tumor stroma.

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[1] Nat Rev Cancer. 2004 Jul;4(7):528-39 - PubMed

[2] Nat Rev Cancer. 2004 Jul;4(7):528-39 - PubMed

[3] Physiol Rev. 1993 Jan;73(1):1-78 - PubMed

[4] Physiol Rev. 1993 Jan;73(1):1-78 - PubMed

[5] Cancer Res. 2007 Oct 1;67(19):9518-27 - PubMed

[6] Cancer Res. 2007 Oct 1;67(19):9518-27 - PubMed

[7] Clin Cancer Res. 2015 Aug 1;21(15):3561-8 - PubMed

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[9] Br J Cancer. 1999 Mar;79(7-8):1133-8 - PubMed

[10] Br J Cancer. 1999 Mar;79(7-8):1133-8 - PubMed

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

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

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