Effective Targeting of the Tumor Microenvironment for Cancer Therapy

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