Abstract 2601: Concomitant treatment of ovarian cell lines with Tumor Treating Fields (TTFields) and PARP inhibitors

Abstract

Abstract Background: PARP inhibitors (PARPi) are an effective treatment option for ovarian cancer patients harboring deleterious BRCA mutations. While such mutations prevail in one third of ovarian cancer patients, most of the other patients gain little survival benefit by the use of PARPi. Tumor Treating Fields (TTFields) are alternating electric fields with antimitotic effects on cancerous cells, also shown to induce a state of BRCAness in several types of cancer cell lines. The current study aimed to explore the potential of combining TTFields with PARP inhibition for the treatment of ovarian cancer in vitro. Methods: Ovarian carcinoma cells A2780 (BRCA1/2 wild type) and OVCAR3 (BRCA1 wild type, BRCA2 deep deletion) were treated with TTFields using the inovitro system. Treatment was applied for 72 h at an intensity of 1.2 V/cm RMS and frequency of 200 kHz. The efficacy of concomitant application of TTFields with the PARP inhibitors niraparib and olaparib was examined via measurements of cell survival, colony forming ability, overall effect (multiplicity product of cytotoxicity and clonogenicity), and apoptosis induction. Results: A2780 or OVCAR3 cells treated with TTFields displayed about 50% reduction in cell counts. Co-application of TTFields with PARPi enhanced the cytotoxic effect compared to that demonstrated by TTFields or PARPi alone. Concomitant application also resulted in reduced clonogenicity, enhanced overall effect, and increased apoptosis. Conclusions: The results suggest potential benefits for TTFields concomitant with PARP inhibiting agents for treatment of ovarian cancer. Citation Format: Antonia Martinez-Conde, Eyal Dor-On, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Concomitant treatment of ovarian cell lines with Tumor Treating Fields (TTFields) and PARP inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2601.