title: Effective targeting of the tumor microenvironment for cancer therapy.
abstract: BACKGROUND
  The tumor microenvironment is an emerging source of novel therapeutic targets in cancer. The glycosaminoglycan hyaluronan (HA) accumulates in 20-30% of tumors and is often associated with poor prognosis.
  
  
  METHODS
  We developed a digitized, semiquantitative scoring system for tumor-associated HA content, then grouped tumors (from animal models or patients) according to the degree of HA accumulation (HA+1,2,3). The antitumor response to HA-depletion by pegylated PH20 hyaluronidase (PEGPH20) was then characterized as a function of HA accumulation.
  
  
  RESULTS
  Semiquantitative grouping of tumors demonstrated that HA accumulation predicts the response of tumors in animal models to PEGPH20. Prospective analysis of HA content was used to predict response to PEGPH20 of squamous cell-type explants from patients with non-small cell lung cancer in nude mice.
  
  
  CONCLUSIONS
  Measurement of HA is a viable biomarker approach for predicting antitumor response in animal models to the HA-depleting agent, PEGPH20.
authors.affiliation: Halozyme Therapeutics, San Diego, CA 94121, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Curtis B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Huang
authors.forename: Flavio
authors.initials: F
authors.lastname: Araiza
authors.forename: Ryan
authors.initials: R
authors.lastname: Osgood
authors.forename: Ge
authors.initials: G
authors.lastname: Wei
authors.forename: Marc
authors.initials: M
authors.lastname: Feldmann
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frost
authors.forename: H Michael
authors.initials: HM
authors.lastname: Shepard
mesh_terms: D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D017931:DNA Primers