Purinergic signaling in ovarian carcinoma

Abstract

Ovarian carcinoma (OC) is the most lethal gynecological cancer worldwide. Around 95% of patients exhibit recurrence five years after treatment; 80% experience recurrence within 18 months after first-line treatment, and progression-free survival rates have not changed over the past 40 years. New therapeutic approaches are imperative to face this complex disease. The purinergic system is a newly recognized element of the tumor microenvironment (TME), as it exhibits a pro-tumor role. Tumor cells release adenosine triphosphate (ATP) into the TME, where it exerts autocrine-paracrine actions that regulate several processes, including the induction of a metastatic phenotype, cell proliferation, and metabolic adaptations. In the extracellular milieu, ATP is converted to adenosine (ADO) by ectonucleotidases (CD39 and CD73), thereby significantly blocking the anti-tumor immune response through interactions with various immune cells. Recent analyses have focused on the diversity and plasticity of purinergic signaling in OC. This review outlines the disease, explains basic concepts of purinergic signaling, and summarizes experimental evidence that indicates purinergic elements may serve as potential targets for novel therapies to overcome OC.

Keywords: Ovarian Carcinoma, Purinergic Receptors, extracellular ATP, Ectonucleotidases, Adenosine