Targeting PARP for the optimal immunotherapy efficiency in gynecologic malignancies

Abstract

Gynecologic cancer, which includes ovarian, cervical, endometrial, vulvar, and vaginal cancer, is a major health concern for women all over the world. Despite the availability of various treatment options, many patients eventually progress to advanced stages and face high mortality rates. PARPi (poly (ADP-ribose) polymerase inhibitor) and immune checkpoint inhibitor (ICI) have both shown significant efficacy in the treatment of advanced and metastatic gynecologic cancer. However, both treatments have limitations, including inevitable resistance and a narrow therapeutic window, making PARPi and ICI combination therapy a promising approach to treating gynecologic malignancies. Preclinical and clinical trials have looked into the combination therapy of PARPi and ICI. PARPi improves ICI efficacy by inducing DNA damage and increasing tumor immunogenicity, resulting in a stronger immune response against cancer cells. ICI, conversly, can increase PARPi sensitivity by priming and activating immune cells, consequently prompting immune cytotoxic effect. Several clinical trials in gynecologic cancer patients have investigated the combination therapy of PARPi and ICI. When compared to monotherapy, the combination of PARPi and ICI increased progression-free survival and overall survival in ovarian cancer patients. The combination therapy has also been studied in other types of gynecologic cancer, including endometrial and cervical cancer, with promising results. Finally, the combination therapeutic strategy of PARPi and ICI is a promising approach in the treatment of gynecologic cancer, particularly advanced and metastatic stages. Preclinical studies and clinical trials have demonstrated the safety and efficacy of this combination therapy in improving patient outcomes and quality of life.

Keywords: Combination therapy; Gynecologic cancer; ICI; Immunotherapy; PARP; PARPi.