Abstract 1691: Tumor treating fields (TTFields) sensitize BRCA wild type pancreatic cancer cells to treatment with FOLFIRINOX

Abstract Background: FOLFIRINOX is a first-line chemotherapy treatment for patients with advanced pancreatic cancer and good performance status. This combination regimen of fluorouracil, oxaliplatin, irinotecan and leucovorin seems to be more effective in BRCA-mutated tumors due to the platinum-based component, acting by the induction of DNA damage. Tumor treating fields (TTFields) are electric fields that disrupt cellular processes crucial for cancer cell viability. TTFields have shown efficacy in preclinical pancreatic cancer models, and to reduce expression of proteins from the BRCA-dependent DNA repair pathway in various cancer types. The current study examined the potential use of TTFields to sensitize BRCA wild-type pancreatic cancer cells to treatment with FOLFIRINOX. Methods: Human pancreatic BRCA wild-type cancer cells BxPC3 and AsPC1 were treated with TTFields, using the inovitro device (Frequency: 150 kHz; Intensity: 0.7 V/cm RMS for BxPC3 cells; 1 V/cm RMS for AsPC1 cells). FOLFIRINOX was administered to the cells at increasing concentrations, with or without co-treatment with TTFields. After 72h of treatment, cell count, colony formation, and apoptosis were measured. For mechanistical insight, RNA was isolated from TTFields-treated and control samples following 24- and 48-hours treatment and examined by RNA-sequencing and real-time PCR. Additionally, protein was isolated from 72-hours treated samples and examined by Western blot. Results: TTFields application to the pancreatic cells together with FOLFIRINOX reduced cell count and colony formation and induced apoptosis relative to FOLFIRINOX or TTFields alone. TTFields downregulated DNA damage repair, DNA replication, and cell cycle related processes, with reduced expression of several central players in the BRCA DNA damage repair pathway. Conclusions: Application of TTFields together with FOLFIRINOX exhibits potential improvement relative to FOLFIRINOX alone in treatment of pancreatic cancer cells lacking background BRCA mutations. This outcome may be rationalized based on downregulation of key DNA repair pathways. Citation Format: Hila Ene, Kerem Ben Meir, Hila Gabay, Rotem Engelman, Eyal Dor-On, Adi Haber, Moshe Giladi, Yoram Palti. Tumor treating fields (TTFields) sensitize BRCA wild type pancreatic cancer cells to treatment with FOLFIRINOX [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 1691.