Abstract 6182: Tumor treating fields (TTFields) concomitant with PARP inhibitors or carboplatin for treatment of ovarian cancer cell lines

Abstract

Abstract Purpose/Objectives: Ovarian cancer continues to be the leading cause of death among gynecological malignancies. Platinum-based chemotherapy is recommended after surgery for most patients with ovarian cancer; and PARP inhibitors (PARPi) are suggested as maintenance therapy. Both therapies induce DNA damage that require the proper activity of the Fanconi Anemia (FA)- BRCA pathway for its resolution, and hence are most beneficial in cancers with a BRCA mutation. However, 75% of patients with ovarian cancer do not harbor BRCA mutations, and thus may experience limited benefit from these treatments. TTFields are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cancer cell death. Recently, TTFields have been shown to induce a state of BRCAness in various cancer types, and to be effective in ovarian cancer pre-clinical models. The objective of the current study was to examine the effect of TTFields concomitant with carboplatin or PARPi on ovarian cancer cell lines. Materials/Methods: A2780 (BRCA wild type) and OVCAR3 (BRCA mutated) ovarian carcinoma cells were treated with TTFields (72 h, 1 V/cm RMS, 200 kHz), alone or with concomitant application of carboplatin or the PARP inhibitors olaparib or niraparib. Efficacy was examined via measurements of cell count, colony formation, and induction of apoptosis. The overall effect was calculated by multiplying cell count with colony formation. Results: Application of TTFields to A2780 or OVCAR3 cells resulted in reduced cell count, increased overall effect, and elevated apoptosis. Carboplatin, olaparib, and niraparib each displayed dose dependent effects in both cell lines, with higher sensitivity demonstrated in the BRCA mutated cells. Concomitant application of TTFields with any of these drugs displayed a synergistic interaction in the BRCA wild type A2780 cells and an additive effect in the BRCA mutant OVCAR-3 cells. Conclusions: The data suggest potential benefits for TTFields concomitant with platinum-based chemotherapy and PARPi in ovarian cancer, even in the absence of background BRCA mutations, in accordance with the BRCAness state induced by TTFields. As such, TTFields may enhance the efficacy of treatment for ovarian cancer in both the adjuvant and maintenance settings. Citation Format: Antonia Martinez-Conde, Hila Ene, Roni Frechtel-Gerzi, Eyal Dor-On, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Tumor treating fields (TTFields) concomitant with PARP inhibitors or carboplatin for treatment of ovarian cancer cell lines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6182.