Antiangiogenic Strategies in Epithelial Ovarian Cancer: Mechanism, Resistance, and Combination Therapy

Abstract

Angiogenesis is one of the hallmarks of cancer and plays a crucial role in carcinogenesis and progression of epithelial ovarian cancer. Antiangiogenic agent is the first approved targeted agent in ovarian cancer. Anti-angiogenic agents mainly include agents target VEGF/VEGFR pathway, such as bevacizumab and agents target receptor tyrosine kinase, and non-VEGF/VEGFR targets of angiogenesis. Antiangiogenic agents demonstrate certain effects in ovarian cancer treatment either as monotherapy or combined with chemotherapy. Unfortunately, antiangiogenic agents, such as bevacizumab, integrated into the ovarian cancer treatment paradigm do not increase cures. Thus, the benefits of anti-angiogenic agents must be carefully weighed against the cost and associated toxicities. Antiangiogenic agents drug resistance and short of predictive biomarkers are main obstacles in ovarian cancer treatment. A combination of poly (ADP-ribose) polymerase inhibitors or immune checkpoint inhibitors might be great strategies to overcome resistance as well as enhance anti-tumor activity of anti-angiogenic drugs. Predictive biomarkers of antiangiogenic agents are in urgent need.

Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

“…During the peritoneal dissemination, addition of genetic mutations and chromosomal aberrations are minimal, whereas the epigenetic dynamics facilitates the phenotypic plasticity of HGSC for adaptation to various microenvironments. Clinical trials for new drugs targeting the peritoneal dissemination of ovarian cancer are in preparation or ongoing [ 16 88 89 90 91 92 93 ] ( Table 1 ). Further studies on the dynamic biology of HGSC cells are needed to develop the epoch-making methods for prevention, early detection, and treatment for HGSC.…”

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity

“…This high mortality is mainly due to diagnoses at advanced stages of the disease (stages III-IV) when the tumor has already spread to the peritoneal cavity and other organs [ 2 ]. Moreover, disease relapse is quite common after primary cytoreductive surgery and a standard platinum/taxane-based chemotherapy [ 3 , 4 ], and after further treatments with different chemotherapeutic agents, such as platinum-derived drugs, antiangiogenic drugs, or PARP inhibitors [ 5 , 6 , 7 ]. Therefore, there is a clear need to develop more therapeutic strategies, such as new drug combinations to overcome resistance and improve ovarian cancer survival.…”

KLHL14: A Novel Prognostic Biomarker and Therapeutic Target for Ovarian Cancer

“…Ovarian cancer is among the most lethal gynaecological malignancies [ 1 ]. It involves a heterogeneous group of malignancies that differ in aetiology, molecular biology, and many other characteristics [ 2 , 3 ].…”