Update on anti-angiogenic agents and PARP inhibitors: is the combination a potential or a reality?

Abstract

Epithelial ovarian cancer (OC) is one of the most common and lethal cancers in women in the developed world. Despite progress in the treatment of OC, most patients experience recurrence within 18 months and long-term survival is low. The development of molecular targeted therapies to complement chemotherapy and surgery has largely focused on inhibition of angiogenesis and interruption of the DNA repair process. Inhibition of angiogenesis is a valuable therapeutic strategy at different points in the treatment pathway, with blockade of the vascular endothelial growth factor VEGF pathway a key target for inhibiting angiogenesis. Targeting the DNA repair processes with inhibitors of poly-ADP ribose polymerase (PARP), particularly in BReast CAncer susceptibility gene (BRCA) mutated tumours, has also shown promising anticancer activity. Prevention of DNA repair and targeting of angiogenesis through PARP inhibition has been extensively explored in OC and significant activity and clinical benefit has been shown with molecularly targeted therapy. Combining anti-angiogenic therapy and PARP inhibitors may offer new therapeutic opportunities in OC, and a number of clinical studies have been exploring the combination of these two molecularly targeted therapies. The identification of reliable predictive markers of response and translational research to establish factors predictive of response to combinations of anti-angiogenic and PARP inhibitor drugs will be required before these therapies can be fully implemented into clinical practice. However, combining anti-angiogenic agents with PARP inhibitors provides new opportunities to improve the treatment options for women with OC.