Abstract A52: Potassium channel activator minoxidil (Rogaine) as a novel single-agent or combination therapy in ovarian cancer

Abstract

Abstract Recent advances in cancer therapy treatments for ovarian cancer have been severely hindered by limited drug availability, excessive side effects, and drug resistance and the difficulty in finding and targeting proteins governing important events in ovarian cancer cells. Novel therapeutic agents targeting specific molecular pathways involved in ovarian cancer are urgently needed. During our investigation to identify new and critical targets in cancer, we found a novel role for the potassium ion channel Kir6.2 in ovarian cancer cells. Our bioinformatics investigation showed that Kir6.2 is expressed in ovarian cancers. We discovered that stimulation of the Kir6.2 channel activity with the small molecule minoxidil (Rogaine®) produces a strong inhibition on ovarian cancer cells’ growth. However, minoxidil had no significant effects on cells that do not express Kir6.2. We describe a biochemical signaling linking activation of Kir6.2 potassium channel to the tumor suppressor mechanism, which includes a Ca2+-dependent production of superoxide species (ROS), which leads to a significant increase of DNA damage. Consequently, cells die upon activation of apoptosis via caspase-3. Minoxidil is an FDA-approved drug that presents very limited side effects. Therefore, our data are important because for the first time they reveal that use of the Kir6.2 potassium channel activator, e.g., Rogaine®, could be considered as a potential single-agent novel treatment for ovarian cancer. Clinicians’ approaches for treating advanced ovarian cancer patients are strongly limited by the concern that current chemotherapeutic agent will raise toxicity. For example, although genotoxic chemotherapeutic agents such as doxorubicin or platinum-containing molecules of carboplatin are among the most effective drug classes in ovarian cancer, dose-dependent toxicity of these agents is often the cause for interrupting the treatment. Our experiments demonstrated that the Kir6.2 activator minoxidil potentiates the antineoplastic effects of doxorubicin as well as of carboplatin by exacerbating their DNA-damaging effects. This discovery is important because it offers the opportunity to design a clinically effective therapeutic strategy in which minoxidil could be administered in combination with genotoxic agents to limit their toxicity in ovarian cancer patients. Citation Format: Daniela Fukushiro-Lopes, Megan Jain, Maryam Khalid, Alexandra Hegel, Saverio Gentile. Potassium channel activator minoxidil (Rogaine) as a novel single-agent or combination therapy in ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A52.