Abstract B035: Tumor Treating Fields (TTFields) together with FOLFIRINOX are effective for the treatment of pancreatic cancer, in vitro and in vivo

Abstract Background: Pancreatic cancer remains a major global health challenge. Despite the use of intensive chemotherapy regimens such as FOLFIRINOX (fluorouracil (5-FU), oxaliplatin, irinotecan and leucovorin) or gemcitabine combined with nab-paclitaxel, treatment outcomes remain poor. Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes crucial for cancer cell viability, approved for the treatment of glioblastoma, pleural mesothelioma, and non-small cell lung cancer (NSCLC). A recent phase 3 trial of TTFields therapy concomitant with gemcitabine and nab-paclitaxel as first-line treatment for unresectable, locally advanced pancreatic adenocarcinoma demonstrated a significant increase in overall survival. The current study examined preclinically the potential use of TTFields to sensitize pancreatic cancer cells to treatment with FOLFIRINOX. Methods: Human pancreatic cancer cells BxPC3 and AsPC1 were treated for 72h with TTFields (150 kHz for both cell lines; 0.7 V/cm RMS for BxPC3 cells; 1 V/cm RMS for AsPC1 cells), using the inovitro device, with or without increasing concentrations of FOLFIRINOX. Cell count, colony formation, and apoptosis were measured. For mechanistical insight, RNA was isolated from control and TTFields-treated samples following 24- and 48-hours treatment, and protein was isolated from 72h treated samples. RNA-sequencing, real-time PCR, and Western blot were employed for sample analysis. In vivo, Panc02 cells were orthotopically inoculated into C57Bl/6 mice. The mice were randomized into four groups: control, TTFields, FOLFIRINOX, and TTFields with FOLFIRINOX. TTFields were applied continuously for 10 days using the inovivo device. FOLFIRINOX was injected the following day, with two consecutive 5-FU administrations the two following days. At the end of the treatment, the tumors were weighed and their volume measured using a caliper. 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. In vivo, significantly reduced tumor weight and volume compared to control was seen in all treatment groups, with the effect for TTFields and FOLFIRINOX most pronounced. Conclusions: Application of TTFields together with FOLFIRINOX exhibits potential improvement relative to FOLFIRINOX alone in treatment of pancreatic cancer cells in vitro and in vivo, potentially due to TTFields-induced downregulation of DNA pathways. Citation Format: Sewar Zbidat, Hila Ene, Mariell Sellevoll, Kerem Ben Meir, Hila Gabay, Eyal Dor-On, Itai Tzchori, Tal Kan, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Tumor Treating Fields (TTFields) together with FOLFIRINOX are effective for the treatment of pancreatic cancer, in vitro and in vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B035.