Efficacy of Tumor Treating Fields (TTFields) in triple negative breast cancer cells and synergy with PARP inhibitor talazoparib
- 1Brown University
Abstract
Breast cancer is the most diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) is a subtype with a poor prognosis because of its aggressiveness and high likelihood of relapse, making its treatment particularly challenging. We explored the effect of Tumor Treating Fields (TTFields) as a novel treatment option for breast cancer, which can be used together with other therapies, such as PARP inhibitors. TTFields use alternating electric fields to inhibit cell growth and induce cellular damage. Our findings indicate that TTFields increase expression of the universal cell cycle CDK inhibitory protein p21(WAF1)/CDKN1A independently of TP53 mutational status. Moreover, when used together with the PARP inhibitor talazoparib, the combination further upregulates p21 protein. Both TTFields alone and together with talazoparib induce cell death as documented by PARP cleavage while reducing markers of cell growth and anti-apoptotic proteins, including p-STAT3, STAT3, and MCL-1. Additionally, TTFields together with talazoparib induce DNA damage, as indicated by increased {gamma}H2AX expression. The combination of talazoparib plus TTFields treatment decrease PDL-1 levels and given its utility in predicting response to PD-1/PD-L1 by mediating immune evasion, this raises the possibility of future combination for immune modulation in cancer therapy. Our preclinical results suggest TTFields alone or together with PARP inhibitors such as talazoparib as a promising therapeutic approach for further development for the treatment of breast cancer.
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BibTeX
@misc{ghandali2026efficacy,
title = {{Efficacy of Tumor Treating Fields (TTFields) in triple negative breast cancer cells and synergy with PARP inhibitor talazoparib}},
author = {M. Ghandali and P. Srinivasan and S. Zhang and Y. Xia and E. T. Wong and C. C. Chen and R. W. Sobol and S. L. Graff and L. Zhou and B. A. Carneiro and Y. Porat and M. Giladi and N. Flint-Brodsly and W. S. El-Deiry},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757989},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757989v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Efficacy of Tumor Treating Fields (TTFields) in triple negative breast cancer cells and synergy with PARP inhibitor talazoparib
AU - M. Ghandali
AU - P. Srinivasan
AU - S. Zhang
AU - Y. Xia
AU - E. T. Wong
AU - C. C. Chen
AU - R. W. Sobol
AU - S. L. Graff
AU - L. Zhou
AU - B. A. Carneiro
AU - Y. Porat
AU - M. Giladi
AU - N. Flint-Brodsly
AU - W. S. El-Deiry
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757989
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757989v1
AB - Breast cancer is the most diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) is a subtype with a poor prognosis because of its aggressiveness and high likelihood of relapse, making its treatment particularly challenging. We explored the effect of Tumor Treating Fields (TTFields) as a novel treatment option for breast cancer, which can be used together with other therapies, such as PARP inhibitors. TTFields use alternating electric fields to inhibit cell growth and induce cellular damage. Our findings indicate that TTFields increase expression of the universal cell cycle CDK inhibitory protein p21(WAF1)/CDKN1A independently of TP53 mutational status. Moreover, when used together with the PARP inhibitor talazoparib, the combination further upregulates p21 protein. Both TTFields alone and together with talazoparib induce cell death as documented by PARP cleavage while reducing markers of cell growth and anti-apoptotic proteins, including p-STAT3, STAT3, and MCL-1. Additionally, TTFields together with talazoparib induce DNA damage, as indicated by increased {gamma}H2AX expression. The combination of talazoparib plus TTFields treatment decrease PDL-1 levels and given its utility in predicting response to PD-1/PD-L1 by mediating immune evasion, this raises the possibility of future combination for immune modulation in cancer therapy. Our preclinical results suggest TTFields alone or together with PARP inhibitors such as talazoparib as a promising therapeutic approach for further development for the treatment of breast cancer.
ER -