Combination of PARPi and anti-PD-L1 therapies in ovarian cancer

Abstract

Ovarian cancer affects one in 72 female patients in America, and nearly half of the females who carry a BRCA1/2 mutation will be diagnosed in their lifetime. At present, treatment options such as immune checkpoint inhibitors (ICI) and poly (ADP-ribose) polymerase inhibitors (PARPi) are effective against ovarian cancer in a subset of the population. In this article, we review important combination therapeutics that maximize the benefits of these agents in as many patients as possible. PARPi targets deoxyribonucleic acid (DNA) repair mechanisms inside malignant cells, inducing cell death through synthetic lethality. ICIs target immunogenic antigens expressed on the surface of malignant cells so that the immune system can eliminate cancer cells. There is a direct relationship between the degree of DNA damage, also known as the tumor mutational burden and the effectiveness of ICIs. This principle suggests that treatments combining PARPi and ICI may allow DNA damage to accumulate by interrupting repair mechanisms, which may result in newly expressed antigens that could be targeted by the bolstered immune system. In addition, heat-shock proteins (Hsps) are upregulated during cellular stress, such as the stress elicited by the immense metabolic demand of cancer cells. Hsp has potential as prognostic biomarkers, and further, study is required to see how they interact with treatment options. More specifically, both Hsp60 and Hsp10 may represent a prognostic biomarker for ovarian cancer, and further, research into their mechanisms is important. ICI and PARPi combinatorial therapies for ovarian cancer may extend the benefits of each drug to a larger population, and Hsp represents an opportunity for predicting outcomes and tracking responses in cancer patients.