Vascular Endothelial Growth Factor Is a Promising ... [Mol Cancer Ther. 2010] - PubMed result

Mol Cancer Ther. 2010 Jul 27. [Epub ahead of print]

Vascular Endothelial Growth Factor Is a Promising Therapeutic Target for the Treatment of Clear Cell Carcinoma of the Ovary.

Mabuchi S, Kawase C, Altomare DA, Morishige K, Hayashi M, Sawada K, Ito K, Terai Y, Nishio Y, Klein-Szanto AJ, Burger RA, Ohmichi M, Testa JR, Kimura T.

Authors' Affiliations: 1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine; 2Department of Obstetrics and Gynecology, Osaka Police Hospital; 3Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan; 4Women's Cancer Program, 5Cancer Genetics and Signaling Program, and 6Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania; and 7Department of Obstetrics and Gynecology, Kansai Rosai Hospital, Amagasaki, Japan.

Abstract

This study examines the role of vascular endothelial growth factor (VEGF) as a therapeutic target in clear cell carcinoma (CCC) of the ovary, which has been regarded as a chemoresistant histologic subtype. Immunohistochemical analysis using tissue microarrays of 98 primary ovarian cancers revealed that VEGF was strongly expressed both in early-stage and advanced-stage CCC of the ovary. In early-stage CCCs, patients who had tumors with high levels of VEGF had significantly shorter survival than those with low levels of VEGF. In vitro experiments revealed that VEGF expression was significantly higher in cisplatin-refractory human CCC cells (RMG1-CR and KOC7C-CR), compared with the respective parental cells (RMG1 and KOC7C) in the presence of cisplatin. In vivo treatment with bevacizumab (Avastin) markedly inhibited the growth of both parental CCC cell-derived (RMG1 and KOC7C) and cisplatin-refractory CCC cell-derived (RMG1-CR and KOC7C-CR) tumors as a result of inhibition of tumor angiogenesis.
The results of the current study indicate that VEGF is frequently expressed and can be a promising therapeutic target in the management of CCC. Bevacizumab may be efficacious not only as a first-line treatment but also as a second-line treatment of recurrent disease in patients previously treated with cisplatin.
Mol Cancer Ther; 9(8); OF1-12. (c)2010 AACR.