Modulated electro-hypertermia enhances the efficancy of anti-cancer drugs in mice with riple-negative breast cancer
Aloss Kenan
Theoretical and Translational Medicine Division
Dr. Kellermayer Miklós
SE Elméleti Orvostudományi Központ, Beznák Aladár terem
2024-10-04 12:00:00
Kórélettan és transzlációs medicina
Dr. Benyó Zoltán
Dr. Hamar Péter
Dr. Micsik Tamás
Dr. Dezső-Tékus Valéria
Dr. Vásárhelyi Barna
Dr. Remport Ádám
Dr. Pohóczky Krisztina
Dr. Cserepes Mihály Tamás
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options. Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). In addition, we explored if mEHT enhances the cancer cell death induced by digoxin.
The LTLD+mEHT combination was more effective at inhibiting tumor growth than free DOX or PLD, as demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the cancer tissue one hour after treatment. Cancer cell damage was associated with an increase in cC3 in the damaged area, and a reduction in Ki67 in the viable tumor. These changes were the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with the various DOX formulation, suggesting no difference in toxicity. In another experiment, mEHT+digoxin combination exhibited stronger tumor inhibitory effects than mEHT or digoxin monotherapy, without signs of toxicity.
However, the results of these studies should be supported by further investigations on mEHT+LTLD and mEHT+digoxin in larger animals, such as pigs. As mEHT, LTLD, and digoxin are under clinical trials, the clinical investigation of these combinations in breast cancer patients is warranted.
