Abstract 4195: Efficacy of tumor treating fields (TTFields) applied with cisplatin and paclitaxel in cervical cancer cells
Authors: Roni Frechtel-Gerzi, Daria Gerasimova, Einav Zeevi, Helena Mumblat, Yara Eid Mutlak, Yuval Shmueli, Roni Monin, Hila Fishman, Inbar Schlachet-Drukerman, Naama Flint-Brodsly, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti, Greg M. Palmer, Angeles Alvarez Secord
Journal: Cancer Research (2025)

Abstract Introduction: Most cervical cancer patients with advanced disease receive first-line cisplatin-based chemotherapy. For late-stage and recurrent cervical cancer, a second chemotherapy may be added, e.g. paclitaxel. Tumor treating fields (TTFields) are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields concomitant with cisplatin or paclitaxel have shown benefit in several tumor types. This study explored the effects of TTFields together with cisplatin and paclitaxel in cervical cancer cells and the underlying mechanism of action of TTFields. Methods: Ca Ski, HeLa and SiHa human cervical cancer cell lines were exposed to TTFields (0.5 or 1 V/cm RMS; 200 kHz; 72 h), in the presence or absence of cisplatin and/or paclitaxel. Cell count, colony formation, and apoptosis were evaluated; and overall effect was calculated as the product of the reductions in cell count and colony formation. TTFields-treated cells were also examined for formation of DNA damage using fluorescent microscopy for γH2AX and for reduced capacity to repair DNA damage via Western blot for proteins from the Fanconi Anemia (FA)-BRCA pathway. The abundance of mitotic spindle defects and chromosome miss-localization was determined by fluorescent staining for α-tubulin and phospho-histone 3 (PH3). Results: TTFields treatment reduced cell count and colony formation in all cervical cancer cell lines tested and augmented the efficacy of cisplatin and paclitaxel. Cells treated with TTFields demonstrated increased levels of DNA damage, reduced expression of DNA repair proteins, and formation of abnormal mitotic figures and chromosome miss-segregation. Conclusions: The preclinical findings suggest benefit for co-treatment of TTFields together with the DNA-damaging agent cisplatin and the anti-mitotic agent paclitaxel. The effects of TTFields are mediated via anti-mitotic and DNA repair impairment mechanisms. Downregulation of the FA-BRCA pathway, required for the repair of cisplatin induced DNA damage, creates conditional vulnerability of the cells that may account for the enhanced efficacy for application of TTFields together with cisplatin. Citation Format: Roni Frechtel-Gerzi, Daria Gerasimova, Einav Zeevi, Helena Mumblat, Yara Eid Mutlak, Yuval Shmueli, Roni Monin, Hila Fishman, Inbar Schlachet-Drukerman, Naama Flint-Brodsly, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti, Greg M. Palmer, Angeles Alvarez Secord. Efficacy of tumor treating fields (TTFields) applied with cisplatin and paclitaxel in cervical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4195.