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Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

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Abstract

Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by anti-angiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies.

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Acknowledgments

Portions of this work were supported by grants from the US National Institutes of Health (P50CA083639, P50CA098258, CA109298, U54 CA151668, CA177909, UH2TR000943, T32CA101642, and CA16672), the Department of Defense (OC120547 and OC093416), a Program Project Development Grant, and an Ann Schreiber-mentored Investigators Award from the Ovarian Cancer Research Fund, CPRIT RP110595, the Bettyann Asche Murray Distinguished Professorship, the Chapman Foundation, the Meyer and Ida Gordon Foundation, the Gilder Foundation, the RGK Foundation, the Judi A. Rees Ovarian Cancer Research Fund, and the Blanton-Davis Ovarian Cancer Research Program. We thank Zachary S. Bohannan, Dawn Chalaire, and Arthur Gelmis for editorial review.

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Choi, HJ., Armaiz Pena, G.N., Pradeep, S. et al. Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches. Cancer Metastasis Rev 34, 19–40 (2015). https://doi.org/10.1007/s10555-014-9538-9

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