Combination Therapy with HSP90 Inhibitors and NanoPulse Stimulation Synergistically Impedes Hepatocellular Carcinoma and Breast Cancer Growth in Mice

Authors

• Christiana Dimitropoulou, Old Dominion UniversityFollow
• Gagan Thangjam, Old Dominion University
• Brittany P. Lassiter, Old Dominion University
• Teresa Hooker, Old Dominion UniversityFollow
• Ruben M. L. Colunga Biancatelli, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• John D. Catravas, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Stephen J. Beebe, Old Dominion UniversityFollow

Document Type

Article

Publication Date

2026

Publication Title

Scientific Reports

Volume

Advance online publication

Pages

1-22

DOI

10.1038/s41598-026-55633-3

Abstract

Nanopulse Stimulation (NPS) represents a promising and innovative therapeutic approach to cancer. Heat shock protein 90 Inhibitors (HI), on the other hand, are currently under investigation in multi-drug chemotherapy trials for various types of malignancies. Here we present results of a combination therapy employing two HSP90 inhibitors (AUY-922 or 17-AAG) and NPS to ablate cancer growth. We firstly tested the inhibitors alone or in combination with NPS in vitro in N1S1 cells, and then into two models of orthotopic Hepatocellular Carcinoma (HCC) and 4T1-Luc breast cancer. NPS + HI reduced tumor growth more than the sum of HI and NPS administered alone, promoting cell death through DNA-damage, PARP activation and caspase-3-mediated apoptosis. Furthermore, HI and NPS, when combined, were used in lower doses than those required to achieve similar results, thus reducing the risk of potential side effects. By acting synergistically, combination therapy with HSP90 Inhibitors and NanoPulse Stimulation acts through distinct mechanisms, demonstrating a potent treatment that results in synergistic tumor mass reduction.

Rights

© The Authors 2026.

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if you modified the licensed material. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "Derived data supporting the findings of this study are available from the corresponding author on request."

Original Publication Citation

Dimitropoulou, C., Thangjam, G., Lassiter, B. P., Hooker, T., Biancatelli, R. M. L. C., Catravas, J. D., & Beebe, S. J. (2026). Combination therapy with HSP90 inhibitors and NanoPulse stimulation synergistically impedes hepatocellular carcinoma and breast cancer growth in mice. Scientific Reports. Advance online publication. https://doi.org/10.1038/s41598-026-55633-3

Repository Citation

Dimitropoulou, Christiana; Thangjam, Gagan; Lassiter, Brittany P.; Hooker, Teresa; Colunga Biancatelli, Ruben M. L.; Catravas, John D.; and Beebe, Stephen J., "Combination Therapy with HSP90 Inhibitors and NanoPulse Stimulation Synergistically Impedes Hepatocellular Carcinoma and Breast Cancer Growth in Mice" (2026). Bioelectrics Publications. 388.
https://digitalcommons.odu.edu/bioelectrics_pubs/388

ORCID

0000-0001-6193-6441 (Lassiter), 0000-0002-1174-3876 (Colunga Biancatelli), 0000-0002-5098-295X (Catravas)