Triple-negative breast cancer (TNBC), comprising approximately 15% of breast cancers, is particularly aggressive, often metastasizing to organs such as the lungs, brain, and bone marrow, leading to poor prognosis and resistance to therapy. Distant metastasis is responsible for most cancer-related deaths. Anthracyclines and taxanes remain the most active chemotherapeutic agents to treat TNBC, often in combination with immunotherapy. Of the taxanes, paclitaxel is widely used. In this abstract, we describe a novel, non-pharmacological, non-contact (i.e. electrode-free) approach that employs low-intensity, non-ionizing electromagnetic (EM) fields that potentiates standard of care (SOC) chemotherapeutic agents’ paclitaxel and capecitabine. Using time-varying magnetic fields to penetrate cell interiors, these induced electric fields (iEFs) selectively alter the actin cytoskeletal machinery in TNBC cells, and significantly reduce their energy required for migration by hampering mitochondrial oxidative phosphorylation through the inhibition of succinate dehydrogenase activity. Importantly, this iEF treatment does not adversely affect normal breast epithelial cells. We show here that iEFs enhance the activity of paclitaxel and capecitabine in inhibiting TNBC growth. Furthermore, combination of anti-migration iEF with cytotoxic paclitaxel or capecitabine is found to hinder migration while also reducing cell viability. Moreover, iEF treatment was instrumental in significantly reducing the IC50 values (half-maximal inhibitory concentration) for paclitaxel (from 13 nM to 6 nM) and for capecitabine (from 1 mM to 0.7 mM) thus potentiating inhibition of cell viability by these cytotoxic agents. RNA sequencing was also performed in the presence and absence of iEF to determine the effect of paclitaxel or capecitabine on gene regulation. The sequencing data revealed that paclitaxel treatment in the presence of iEF upregulated 1058 genes and down regulated 1126 genes when compared to TNBC cells treated with paclitaxel in the absence of iEF. Collectively, our results show that iEF enhances the efficacy of chemotherapeutic agents’ paclitaxel and capecitabine in inhibiting TNBC growth, viability, migration in addition to affecting the gene expression pattern. This work represents a critical step in improving current SOC for patients with TNBC for whom there are limited options. (This work is supported by DOD: W81XWH2010065, and Division of Medical Oncology award, OSU for Eswar Shankar)Citation Format:Gautam Sarathy, Shivani Dhekni, Arya Mariam Roy, Margaret Gatti-Mays, Vish Subramaniam, Eswar Shankar. Enhancing chemotherapeutic activity against triple-negative breast cancer cells using induced electric fields [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4403.
