TY - JOUR
T1 - Targeting the tumor microenvironment in cancer
T2 - Why hyaluronidase deserves a second look
AU - Whatcott, Clifford J.
AU - Han, Haiyong
AU - Posner, Richard G.
AU - Hostetter, Galen
AU - Von Hoff, Daniel D.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84859983619&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859983619&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-11-0136
DO - 10.1158/2159-8290.CD-11-0136
M3 - Article
C2 - 22053288
AN - SCOPUS:84859983619
SN - 2159-8274
VL - 1
SP - 291
EP - 296
JO - Cancer Discovery
JF - Cancer Discovery
IS - 4
ER -