Ueda Taeko
   Department   School of Medicine  Obstetrics and Gynecology, Clinical Medical Sciences
   Position  
Article types journal article
Language English
Peer review Peer reviewed
Title Targeting the heparin-binding epidermal growth factor-like growth factor in ovarian cancer therapy.
Journal Formal name:Current opinion in obstetrics & gynecology
Abbreviation:Curr Opin Obstet Gynecol
ISSN code:1473656X/1040872X
Domestic / ForeginForegin
Volume, Issue, Page 23(1),24-30頁
Author and coauthor Tsujioka Hiroshi, Yotsumoto Fusanori, Hikita Shoko, Ueda Taeko, Kuroki Masahide, Miyamoto Shingo
Publication date 2011/02
Summary PURPOSE OF REVIEW:Therapeutics targeting the ErbB protein family receptors have not always yielded favorable or successful results in present cancer therapy. This review discusses the possibility of the clinical adaptation of targeting against heparin-binding epidermal growth factor-like growth factor (HB-EGF), one of the ligands of the ErbB system, in ovarian cancer therapy.RECENT FINDINGS:We have previously described the results of studies concerning roles of HB-EGF in tumor formation in ovarian cancer. In brief, lisophosphatidic acid (LPA) and HB-EGF are predominantly expressed in advanced ovarian cancer, and LPA-induced, a disintegrin and metalloprotease-mediated ectodomain shedding of HB-EGF was found to be critical to tumor formation. We also noted that exogenous expression of HB-EGF enhanced tumor formation but inhibition blocked both extracellular signal-related kinase and serine/threonine protein kinase activation. Finally we investigated the antitumor effects of CRM197 - a specific HB-EGF inhibitor - on ovarian cancer cells by evaluating human ovarian cancer cell proliferation.SUMMARY:We discuss alternative strategies to develop the chemotherapeutic agent based on targeting ErbB family ligands rather than their receptors. A phase I study of CRM197 for advanced ovarian cancer has already begun, which is the first approved trial of ErbB-ligand-targeted therapy. We also discuss clinical adaptations based on combination of CRM197 with other conventional chemotherapeutic agents.
DOI 10.1097/GCO.0b013e3283409c91
PMID 20966750