Utility of Vascular Endothelial Growth Factor Inhibitors in the Treatment of Ovarian Cancer: from Concept to Application

Overview

Journal J Oncol

Specialty Oncology

Date 2011 Oct 1

PMID 21961001

Citations 5

Authors

Afshin Amini

Samar Masoumi Moghaddam

David L Morris

Mohammad H Pourgholami

Affiliations

Soon will be listed here.

Abstract

Despite recent advances in the management of ovarian cancer, it remains the most lethal gynecologic malignancy. Vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in the progression of ovarian cancer leading to the eventual development of malignant ascites. On this basis, agents rendering VEGF ineffective by neutralizing VEGF (bevacizumab), blocking its receptors (aflibercept), or interfering with the postreceptor signaling pathways (sunitinib) provide us with the rational treatment options. These agents are generally used in combination with the standard chemotherapeutic drugs. Here, we discuss the basis of and the logic behind the use of these agents in the treatment of epithelial ovarian cancer, as well as their evaluation in different preclinical and clinical studies.

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References

Thigpen T, Stuart G, Bois A, Friedlander M, Fujiwara K, Guastalla J . Clinical trials in ovarian carcinoma: requirements for standard approaches and regimens. Ann Oncol. 2005; 16 Suppl 8:viii13-viii19. DOI: 10.1093/annonc/mdi962. View

Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T . Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling. Cancer Sci. 2010; 101(12):2658-63. PMC: 11159119. DOI: 10.1111/j.1349-7006.2010.01736.x. View

Pourgholami M, Cai Z, Badar S, Wangoo K, Poruchynsky M, Morris D . Potent inhibition of tumoral hypoxia-inducible factor 1alpha by albendazole. BMC Cancer. 2010; 10:143. PMC: 2873385. DOI: 10.1186/1471-2407-10-143. View

Morabito A, Piccirillo M, Falasconi F, De Feo G, Del Giudice A, Bryce J . Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. Oncologist. 2009; 14(4):378-90. DOI: 10.1634/theoncologist.2008-0261. View

Barrena Medel N, Wright J, Herzog T . Targeted therapies in epithelial ovarian cancer. J Oncol. 2010; 2010:314326. PMC: 2810474. DOI: 10.1155/2010/314326. View

Pourgholami M, Cai Z, Lu Y, Wang L, Morris D . Albendazole: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation in OVCAR-3 tumor-bearing nude mice. Clin Cancer Res. 2006; 12(6):1928-35. DOI: 10.1158/1078-0432.CCR-05-1181. View

Loges S, Mazzone M, Hohensinner P, Carmeliet P . Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell. 2009; 15(3):167-70. DOI: 10.1016/j.ccr.2009.02.007. View

Spratlin J, Cohen R, Eadens M, Gore L, Camidge D, Diab S . Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010; 28(5):780-7. PMC: 2834394. DOI: 10.1200/JCO.2009.23.7537. View

Wright J, Hagemann A, Rader J, Viviano D, Gibb R, Norris L . Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: A retrospective analysis. Cancer. 2006; 107(1):83-9. DOI: 10.1002/cncr.21969. View

10.

Matei D, Sill M, Lankes H, DeGeest K, Bristow R, Mutch D . Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. J Clin Oncol. 2010; 29(1):69-75. PMC: 3055861. DOI: 10.1200/JCO.2009.26.7856. View

11.

Matulonis U, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C . Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol. 2009; 27(33):5601-6. PMC: 2792954. DOI: 10.1200/JCO.2009.23.2777. View

12.

Spannuth W, Nick A, Jennings N, Armaiz-Pena G, Mangala L, Danes C . Functional significance of VEGFR-2 on ovarian cancer cells. Int J Cancer. 2008; 124(5):1045-53. PMC: 2668132. DOI: 10.1002/ijc.24028. View

13.

Schumacher J, Dings R, Cosin J, Subramanian I, Auersperg N, Ramakrishnan S . Modulation of angiogenic phenotype alters tumorigenicity in rat ovarian epithelial cells. Cancer Res. 2007; 67(8):3683-90. DOI: 10.1158/0008-5472.CAN-06-3608. View

14.

Chura J, Van Iseghem K, Downs Jr L, Carson L, Judson P . Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynecol Oncol. 2007; 107(2):326-30. DOI: 10.1016/j.ygyno.2007.07.017. View

15.

Ebos J, Lee C, Cruz-Munoz W, Bjarnason G, Christensen J, Kerbel R . Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009; 15(3):232-9. PMC: 4540346. DOI: 10.1016/j.ccr.2009.01.021. View

16.

Campos S, Penson R, Matulonis U, Horowitz N, Whalen C, Pereira L . A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma. Gynecol Oncol. 2012; 128(2):215-20. DOI: 10.1016/j.ygyno.2012.07.126. View

17.

Zhang A, Meng L, Wang Q, Xi L, Chen G, Wang S . Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2. Oncol Rep. 2006; 15(4):831-6. View

18.

Richardson D, Backes F, Seamon L, Zanagnolo V, OMalley D, Cohn D . Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer. Gynecol Oncol. 2008; 111(3):461-6. DOI: 10.1016/j.ygyno.2008.08.011. View

19.

Sonmezer M, Gungor M, Ensari A, Ortac F . Prognostic significance of tumor angiogenesis in epithelial ovarian cancer: in association with transforming growth factor beta and vascular endothelial growth factor. Int J Gynecol Cancer. 2004; 14(1):82-8. DOI: 10.1111/j.1048-891x.2004.14202.x. View

20.

Annunziata C, Walker A, Minasian L, Yu M, Kotz H, Wood B . Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res. 2010; 16(2):664-72. PMC: 2943831. DOI: 10.1158/1078-0432.CCR-09-2308. View