Combinatorial therapy of immune checkpoint and cancer pathways provides a novel perspective on ovarian cancer treatment

Oncol Lett. 2019 Mar;17(3):2583-2591. doi: 10.3892/ol.2019.9902. Epub 2019 Jan 8.

Abstract

An increasing number of studies have reported that immunotherapy serves a significant role in ovarian cancer treatment. In recent years, blockade of checkpoint pathways, including programmed death-ligand 1 (PD-L1)/programmed death-1 and cytotoxic T-lymphocyte-associated protein 4, has demonstrated significant clinical and preclinical benefits in the treatment of ovarian cancer. Additionally, tumor-associated angiogenesis and homologous recombination deficiency frequently occurs in patients with high-grade ovarian cancer, which makes cancer cells more susceptible to targeted therapies, including therapies targeting poly (ADP-ribose) polymerase inhibitor, and anti-angiogenic approaches. Additionally, targeted therapy has been associated with elevated PD-L1 expression in tumor cells, increased T-cell infiltration in tumors and dendritic cell stimulation. This synergistic effect provides the rationale for the joint application of targeted therapy and immunotherapy. Checkpoint blockades are able to elicit durable antitumor immune reactions and complement the transient antitumor effect of targeted therapies. The current review discusses the underlying mechanism of these therapies and novel developments in combined therapy for the treatment of ovarian cancer.

Keywords: anti-angiogenesis; cytotoxic T-lymphocyte-associated protein 4; ovarian cancer; poly (ADP-ribose) polymerase inhibitor; programmed death 1; programmed death-ligand 1; vascular endothelial growth factor.

Publication types

  • Review