Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors

Abstract

Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases. While these agents have an established role in ovarian cancer treatment strategy in BRCA mutated and homologous recombination deficient patients, an appropriate predictive molecular test to select patients is lacking in clinical practice. At the same time, the impressive results of immunotherapy in other malignancies, have opened the space for the introduction of immune-stimulatory drugs in ovarian cancer. Despite immune checkpoint inhibitors as a monotherapy bringing only modest efficacy when assessed in pretreated ovarian cancer patients, the combination with chemotherapy, anti-angiogenetics, PARP inhibitors, and radiotherapy is believed to warrant further investigation. We reviewed literature evidence on PARP inhibitors and immunotherapy in ovarian cancer treatment.

A Novel Monoclonal Antibody Targeting Cancer-Specific Plectin Has Potent Antitumor Activity in Ovarian Cancer

“…Under current treatment regimens, OC has an overall cure rate of less than 40% across all stages, illustrating the need for more effective treatment modalities [ 28 ]. Predominant OC targeted therapies, consisting of VEGF (bevacizumab) and PARP inhibitors (olaparib), have significant limitations [ 57 , 58 , 59 ]. For example, anti-VEGF therapy displays toxic side effects such as hypertension and gastrointestinal perforation in OC patients due to VEGF playing a critical role in normal physiological processes [ 60 ].…”

Immune-Related Long Non-coding RNA Constructs a Prognostic Signature of Ovarian Cancer

“…It is concerned that due to the immunotherapy as a monotherapy have the unsatisfactory results, accumulated evidence indicates the clinical efficacy of combining appropriate dose of chemotherapies with ICIs [42]. It is necessary to explore the combination of immunotherapy and chemotherapy or PARP inhibitors in OC [43,44]. Our predictive signature can be used to analyze the sensitivity of chemotherapy and immunotherapy in different risk groups, which may provide a potential possibility for the combination of these two kinds of therapy strategies in OC.…”

Immune-Related Long Non-Coding RNA Constructs a Prognostic Signature of Ovarian Cancer

“…It is concerned that due to the immunotherapy as a monotherapy have the unsatisfactory results, accumulated evidence indicates the clinical e cacy of combining appropriate dose of chemotherapies with ICIs (31). It is necessary to explore the combination of immunotherapy and chemotherapy or PARP inhibitors in ovarian cancer (32,33). Our predictive signature can be used to analyze the sensitivity of chemotherapy and immunotherapy in different risk groups, which may provide a potential possibility for the combination of these two kinds of therapy strategies in ovarian cancer.…”