Combination therapy of zibotentan with cisplatinum and paclitaxel is an effective regimen for epithelial ovarian cancer

Canadian Journal of Physiology and Pharmacology
Laura RosanòAnna Bagnato

Abstract

In human ovarian carcinoma, the endothelin-1 (ET-1) / endothelin A receptor (ETAR) axis is overexpressed, correlating with tumor grade. Moreover, ETAR activation by ET-1 affects cell proliferation, survival, angiogenesis, and invasion. ETAR blockade with zibotentan (ZD4054), a specific ETAR antagonist, significantly inhibits ovarian cancer growth in vitro and in vivo, underscoring the relevance of this pathway as a target for cancer therapy. Since clinical trial results have defined the combination of platinum and taxane as the standard of care in the management of ovarian cancer, here we explored the therapeutic efficacy of the integration of zibotentan with cytotoxic drugs having different modes of action. We found that the combination of zibotentan with cisplatinum as well as zibotentan with paclitaxel was more effective at inhibiting ovarian cancer HEY cell proliferation induced by endogenous ET-1 than were the single agents alone. However, a significantly enhanced efficacy was observed when we combined zibotentan, cisplatinum, and paclitaxel. Accordingly, in HEY xenografts the coadministration of zibotentan with cisplatinum enhanced the efficacy of the cytotoxic drug alone in controlling tumor growth, associated with reduc...Continue Reading

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Nov 14, 2000·The American Journal of Pathology·D SalaniA Bagnato
Jul 20, 2005·Neoplasia : an International Journal for Oncology Research·Joel B NelsonBeth R Pflug
Dec 3, 2005·Endocrine-related Cancer·Anna BagnatoLaura Rosanò
Sep 21, 2006·Neoplasia : an International Journal for Oncology Research·Ardavan AkhavanBeth R Pflug
Mar 8, 2008·The International Journal of Biochemistry & Cell Biology·Anna Bagnato, Laura Rosanò
Sep 2, 2008·Canadian Journal of Physiology and Pharmacology·Anna BagnatoLaura Rosanò
May 23, 2009·Nature Reviews. Cancer·Robert C BastGordon B Mills
Oct 2, 2009·Lancet·Bryan T HennessyMaurie Markman

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Citations

Jun 15, 2011·Drugs·Roshni KalachandMaurie Markman
Aug 5, 2016·International Journal of Molecular Sciences·Qiao ZhangYanjiang Qiao
Apr 20, 2013·Oncology Letters·Xiao-Yu PanXin Yang
Jan 12, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura RosanòAnna Bagnato

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