Abstract B071: Tumor Treating Fields (TTFields) together with PARP inhibitors for treatment of pancreatic cancer cells

Abstract

Abstract Purpose/Objectives: Pancreatic cancer remains a leading cause of cancer-related death, with limited treatment options available for the advanced stage. PARP inhibitors (PARPi) are effective treatment options in patients with germline BRCA mutations. Recently, TTFields – electric fields that disrupt cellular processes critical for cancer cell viability – have been shown to induce a state of BRCAness in various cancer types. The objective of this study was to examine possible sensitization of BRCA wild type pancreatic cancer cell lines to PARP inhibition by the application of TTFields. Materials/Methods: BxPC3 and AsPC1 BRCA wild type, human pancreatic cancer cells were treated for 48 and 72 h, respectively, with TTFields (intensity of 1 and 0.7 V/cm RMS, respectively) at a frequency of 150 kHz using the inovitro device. TTFields were applied to the cells alone or together with various concentrations of the PARP inhibitors niraparib or olaparib. Cell count, colony formation, and apoptosis were measured at treatment end. Results: Applying TTFields to pancreatic cell lines resulted in cytotoxicity, anti-clonogenic effect, and induction of apoptosis. PARP inhibitors also demonstrated such effects, in a dose-dependent fashion. Co-application of TTFields enhanced the effects of PARP inhibitors. Conclusions: The results show a benefit for concomitant application of TTFields and PARPi in pancreatic cancer, potentially due to the BRCAness state induced by TTFields. The data suggest TTFields may enhance PARP inhibition efficacy in the absence of background BRCA mutations. Citation Format: Antonia Martinez-Conde, Hila Ene, Kerem Ben-Meir, Eyal Dor-On, Puru Lamichhane, Adi Haber, Moshe Giladi, Yoram Palti. Tumor Treating Fields (TTFields) together with PARP inhibitors for treatment of pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B071.