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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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Journal Article
Targeting the Tumor Stroma: the Biology and Clinical Development of Pegylated Recombinant Human Hyaluronidase (PEGPH20)
2017
Overview
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.
Publisher
Springer US,Springer Nature B.V
Subject
/ Adenocarcinoma - drug therapy
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - isolation & purification
/ Carcinogenesis - drug effects
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - pathology
/ Evolving Therapies (R Bukowski
/ Extracellular Matrix - genetics
/ Extracellular Matrix - metabolism
/ Humans
/ Hyaluronic Acid - isolation & purification
/ Hyaluronoglucosaminidase - genetics
/ Hyaluronoglucosaminidase - therapeutic use
/ Medicine
/ Oncology
/ Pancreas
/ Pressure
/ Recombinant Proteins - genetics
/ Recombinant Proteins - therapeutic use
/ Stroma
/ Stromal Cells - drug effects
/ Topical Collection on Evolving Therapies
/ Tumors
