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. MATERIALS AND 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. CONCLUSION:Measurement of HA is a viable biomarker approach for predicting antitumor response in animal models to the HA-depleting agent, PEGPH20.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Jiang P,Li X,Thompson CB,Huang Z,Araiza F,Osgood R,Wei G,Feldmann M,Frost GI,Shepard HM

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

1203-12

issue

4

eissn

0250-7005

issn

1791-7530

pii

32/4/1203

journal_volume

32

pub_type

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