Targeting PD-1/PD-L1 axis as new horizon for ovarian cancer therapy

Abstract

Ovarian cancer is one of the deadliest gynecological cancers and the 7th most commonly occurring cancer in women globally. The 5 year survival rate is estimated to be less than 25 %, as in most cases, diagnosis occurs at an advanced stage. Despite recent advancements in treatment, clinical outcomes still remain poor, thus implicating the need for urgent identification of novel therapeutics for the treatment of this cancer. Ovarian cancer is considered a low immune reactive cancer as the tumor cells express insufficient neoantigens to be recognized by the immune cells and thus tend to escape from immune surveillance. Thus, in the recent decade, immunotherapy has gained significant attention and has rejuvenated the understanding of immune regulation in tumor biology. One of the critical immune checkpoints is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. Engagement of PD-1 to PD-L1 promotes immunologic tolerance and suppresses the effector T cells and maintains tumor Tregs, thus playing a crucial role in enhancing tumor survival. Recent studies are targeted to develop inhibitors that block this signal to augment the anti-tumor activity of immune cells. Also, compared to monotherapy, the combinatorial treatment of immune checkpoint inhibitors with small molecule inhibitors have shown promising results with improved efficacy and acceptable adverse events. The present review provides an overview of the PD-1/PD-L1 axis and role of non-coding RNAs in regulating this axis. Moreover, we have highlighted the various preclinical and clinical investigations on PD-1/PD-L1 immune checkpoint inhibitors and have discussed the limitations of immunotherapies in ovarian cancer.

Keywords: Immune checkpoint; Immunotherapy; Inhibitors; Ovarian cancer; PD-1/PD-L1.