Title:Novel Therapeutic Strategies For Angiogenesis Inhibition In Recurrent Ovarian Cancer
Volume: 3
Issue: 4
Author(s): Victoria L. Chiou, Elise C. Kohn, Nicole Davarpanah and Jung-Min Lee
Affiliation:
Keywords:
Angiogenesis, antiangiogenic, immunotherapy, ovarian cancer, PARP inhibitor, VEGF.
Abstract: 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.
