Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look

Cancer Discov. 2011 Sep;1(4):291-6. doi: 10.1158/2159-8290.CD-11-0136.


Increased extracellular matrix (ECM) deposition is a characteristic observed in many solid tumors. Increased levels of one ECM component-namely, hyaluronan (HA)-leads to reduced elasticity of tumor tissue and increased interstitial fluid pressure. Multiple initial reports showed that the addition of hyaluronidase (HYAL) to chemotherapeutic regimens could greatly improve efficacy. Unfortunately, the bovine HYAL used in those studies was limited therapeutically by immunologic responses to treatment. Newly developed recombinant human HYAL has recently been introduced into clinical trials. In this article, we describe the role of HA in cancer, methods of targeting HA, and clinical studies performed to date, and we propose that targeting HA could now be an effective treatment option for patients with many different types of solid tumors.

Keywords: cancer; extracellular matrix; hyaluronan; hyaluronidase; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism*
  • Humans
  • Hyaluronic Acid / metabolism*
  • Hyaluronoglucosaminidase / metabolism*
  • Hyaluronoglucosaminidase / pharmacology
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Recombinant Proteins / pharmacology
  • Tumor Microenvironment / drug effects*


  • Recombinant Proteins
  • Hyaluronic Acid
  • Hyaluronoglucosaminidase