Combination therapy with HSP90 inhibitors and NanoPulse stimulation synergistically impedes hepatocellular carcinoma and breast cancer growth in mice.

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.