Novel Therapeutic Strategies For Angiogenesis Inhibition In Recurrent Ovarian Cancer

Angiogenesis plays a vital role in ovarian carcinogenesis and has become an important therapeutic target of ovarian cancer. Insights into the genomic complexity of ovarian cancer and modest single-agent activity of targeted agents have led to testing of biologic agent combinations in order to leverage modulation of potentially interactive targets. Many studies have added angiogenesis inhibitors to chemotherapy in ovarian cancer, with progression-free survival improvements only. Novel angiogenesis inhibitor combinations that reflect the science of ovarian cancer are needed. An exciting new direction is the interaction between angiogenesis and DNA damage repair pathways, as both pathways are active therapeutic targets in ovarian cancer. Preclinical studies demonstrate an interaction between hypoxia and inhibition of DNA damage repair. γH2AX, a marker of DNA damage response activation, is necessary for endothelial cell proliferation under hypoxia and in hypoxia-driven neovascularization in vivo. The successful combination of a vascular endothelial growth factor receptor inhibitor and a poly (ADP-ribose) polymerase inhibitor in recent clinical trials has suggested this direction can be an important advance. Further clinical combination strategies of angiogenesis inhibition and other pathways including DNA damage repair pathways are currently in development for treatment of recurrent ovarian cancer.