Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.
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 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.
Mabuchi
Seiji
S
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. smabuchi@gyne.med.osaka-u.ac.jp
Kawase
Chiaki
C
Altomare
Deborah A
DA
Morishige
Kenichirou
K
Hayashi
Masami
M
Sawada
Kenjiro
K
Ito
Kimihiko
K
Terai
Yoshito
Y
Nishio
Yukihiro
Y
Klein-Szanto
Andres J
AJ
Burger
Robert A
RA
Ohmichi
Masahide
M
Testa
Joseph R
JR
Kimura
Tadashi
T
D018262:Adenocarcinoma, Clear Cell / Q000473:pathology / Q000628:therapy*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000473:pathology / Q000628:therapy; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042442:Vascular Endothelial Growth Factors; D000068258:Bevacizumab; D002945:Cisplatin