PhD Scientific Days 2025

Theoretical and Translational Medicine II.

Reviving Hormonal Signaling: Modulated Electro-Hyperthermia (mEHT)-Driven Progesterone Receptor Re-Expression in Triple-Negative Breast Cancer Mouse Model and Antiprogestin Potentiation for Targeted Therapy

Előadó neve

Dr. Leroy Viana Pedro Henrique

Neptun code

GKEDSP

Előadó munkahelye

Semmelweis University

Előadó telefonszáma

+36702138189

Előadó e-mail címe

leroy.viana.pedro.henrique@semmelweis.hu

Az előadás címe

Reviving Hormonal Signaling: Modulated Electro-Hyperthermia (mEHT)-Driven Progesterone Receptor Re-Expression in Triple-Negative Breast Cancer Mouse Model and Antiprogestin Potentiation for Targeted Therapy

Szerző(k) neve és munkahelye

Pedro Henrique Leroy Viana¹, Csaba Schvarcz¹, Lea Danics¹, Balázs Besztercei¹, Zoltán Koós¹, Dániel Bocsi¹, Zoltán Benyó¹, Péter Hamar¹

1: Semmelweis University

Bemutatás módja

Szóbeli

Szekció

Theoretical and Translational Medicine II.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction:
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking hormone receptors, including the progesterone receptor (PR), which limits treatment options and contributes to poor prognosis. PR plays a key role in hormone-driven tumor progression, and its absence in TNBC is linked to therapy resistance and enhanced aggressiveness. Modulated electro-hyperthermia (mEHT), a treatment combining electromagnetic fields and localized heat, has emerged as a promising strategy to induce tumor-specific cytotoxicity. Epigenetic regulators such as DNMTs and HDACs are known to silence PR expression, but the reversible nature of these modifications offers opportunities to reprogram cancer cells.

Aims:
This study aims to investigate whether mEHT can restore PR expression in TNBC and sensitize tumors to selective progesterone receptor modulators (SPRMs), offering a novel therapeutic approach.

Method:
TNBC mouse models were treated with mEHT. Multiplex gene expression profiling using next-generation sequencing (NGS) and NanoString was conducted. PR expression was further validated using RT-qPCR, immunohistochemistry, and Western blot. Epigenetic modulators associated with hyperthermia (DNMT3a, HDAC6/7/8) were analyzed. The effect of SPRMs, such as mifepristone (MIF), was evaluated both in vitro and in vivo.

Results:
mEHT significantly upregulated PR expression at both gene and protein levels. Epigenetic profiling showed decreased expression of specific HDACs and DNMT3a in mEHT-treated tumors. Re-expression of PR made TNBC cells responsive to SPRMs, particularly mifepristone, suggesting therapeutic efficacy in preclinical models.

Conclusion:
Our findings indicate that mEHT can restore functional PR expression in TNBC and re-sensitize tumors to antiprogestins, offering a new direction for targeted therapy in receptor-negative breast cancers.

Funding:
2024-2.1.1-EKÖP
OTKA_K, 145998-NKFI

University

Semmelweis University

Supervisor

Péter Hamar

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

6868

Start

12:15

End

12:30