Abstract A42: Potassium channel activity unveils ovarian cancer vulnerability: From signaling to precision medicine

Abstract

Abstract Decades of studies on ion channels have vastly demonstrated the critical functions of these proteins in many physiologic and pathologic conditions. Also, studies on ion channels have provided for an extraordinary pharmacopeia of useful compounds, often with selective actions and minimal side effects. Nevertheless, the function of ion channels in controlling cancer biology is still unknown and underexplored. Our research demonstrates that the Kir6.2/SUR2 potassium ion channel can be a prognostic factor in gynecologic cancers. Here we present data showing that the Kir6.2/SUR2 channel activity control biochemical pathways underlying proliferation and metabolism in gynecologic cancers, including endometrioid and high-grade serous ovarian cancer. Use of activators of the Kir6.2/SUR2 produced an arrest of the cell cycle, a significant mitochondrial dysfunction that is associated with alteration of the oxidative cellular state and DNA damage in cisplatin-resistant ovarian cancer. Also, our in vivo experiments show the antigrowth effects of pharmacologically targeting Kir6.2/SUR2 on ovarian cancer with FDA-approved molecules. This study offers the opportunity to consider the therapeutic benefits of repurposing drugs targeting the Kir6.2/SUR2 channel for a treatment of gynecologic cancers that is efficient and safe. Citation Format: Daniela Fukushiro Lopes, Alexandra Hegel, Vitaly Senyuk, Angela Russo, Margaret Liotta, Ronald Potkul, Craig Beeson, Joanna Brurgette, Saverio Gentile. Potassium channel activity unveils ovarian cancer vulnerability: From signaling to precision medicine [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A42.