Abstract B027: Preclinical efficacy of Tumor Treating Fields (TTFields) applied with PARP inhibitors or carboplatin in ovarian cancer

Abstract

Abstract Purpose: Ovarian cancer is the leading cause of death among cancers of the female reproductive system. Surgery and platinum-based adjuvant chemotherapy followed by PARP inhibitor (PARPi) maintenance therapy is standard treatment for most patients diagnosed with ovarian cancer. The mechanism of action of PARPi and platinum-based therapy involves the induction of DNA damage, which requires the Fanconi Anemia (FA)- BRCA pathway for repair, making these agents most beneficial in cancers with BRCA mutations. However, 75% of patients with ovarian cancer have BRCA wild type tumors and therefore their benefit from PARPi is limited. TTFields are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cancer cell death. Recent research demonstrated TTFields induce a state of BRCAness in multiple cancer types, as well as anticancer effects in ovarian cancer preclinical models. This study investigated the impact of TTFields concomitant with carboplatin or PARPi in ovarian cancer cell lines. Methods: A2780 (BRCA wild type), OVCAR3 (BRCA mutated), and A2780cis (platinum-resistant) ovarian cancer cells were treated with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or concomitant with application of carboplatin or a PARPi (olaparib or niraparib). Efficacy assessments included cell count, colony formation, and apoptosis induction. The overall effect was calculated by multiplying the effects on cell count and colony formation. Results: TTFields treatment reduced cell count, increased overall effect, and elevated apoptosis. Carboplatin, olaparib, and niraparib exhibited dose-dependent effects in all cell lines. When TTFields were applied together with these drugs, a synergistic interaction was observed in the BRCA wild-type A2780 cells and platinum-resistant A2780cis cells, while an additive effect was noted in the BRCA mutant OVCAR-3 cells. Conclusions: This data implies potential advantages for TTFields concomitant with platinum-based chemotherapy and PARPi in ovarian cancer, even without underlying BRCA mutations. This aligns with the BRCAness state induced by TTFields and suggests a benefit in platinum resistant cancer. Overall, TTFields may augment the efficacy of ovarian cancer treatment in both adjuvant and maintenance settings. Citation Format: Antonia Martinez-Conde, Hila Ene, Kerem Ben-Meir, Roni Frechtel-Gerzi, Eyal Dor-On, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Preclinical efficacy of Tumor Treating Fields (TTFields) applied with PARP inhibitors or carboplatin in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B027.