Abstract 2865: Repurposing potassium channel blockers to target metastasis in triple negative breast cancer

Abstract

Abstract Despite the identification of pro-metastatic markers and signaling pathways that drive the invasion of triple negative breast cancer (TNBC), there are currently no treatments that directly target invading cells. Recent evidence suggests that the bioelectric state of cancer cells can drive cell proliferation and invasion, creating an opportunity to investigate new therapies that target the bioelectric state of a cell. Our previous data suggests that of the most abundant ions present in the body, potassium (K+) is most important for controlling the bioelectric state of TNBC cells, and that K+ flux affects the invasive properties of TNBC cells. Therefore, we hypothesized that blocking K+ channels would disrupt the bioelectric state and reduce 2D migration and 3D invasion. Four FDA-approved K+ channel blockers (amiodarone, carvedilol, imipramine, and thioridazine) were selected from the Repurposing Drugs in Oncology database based on inhibition target channels and mechanisms of action. Cell viability in human TNBC MDA-MB-231 and MDA-MB-468 cells was investigated and IC50 dose response curves were generated to determine that 5 µM and 10µM were the optimal doses to study further. Interestingly, while we determined that all four drugs reduced cell viability, amiodarone and carvedilol significantly changed the bioelectric state and reduced proliferation of TNBC cells compared to negative controls. Experiments are ongoing to evaluate the effects of these inhibitors on 2D migration, 3D invasion, and in an in vivo mouse xenograft study. Understanding the mechanism behind K+ channel inhibition in TNBC could give rise to new pharmacologic targets. In addition, supplementing existing metastatic TNBC regimens with a repurposed K+ channel blocker could potentially reduce development costs, decrease time to market, and provide a new treatment option to patients. Citation Format: Priyanka Ram, Samantha L. Payne, Madeleine J. Oudin. Repurposing potassium channel blockers to target metastasis in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2865.