Abstract 3109: Pre-clinical efficacy of tumor treating fields and imipridones in glioblastoma and colorectal cancer cell lines

Tumor treating fields (TTFields) utilize alternating electric fields of intermediate frequency and low intensity to disrupt cell division, demonstrating strong promise for tumor treatment. Currently, TTFields are approved for glioblastoma, unresectable mesothelioma and metastatic non-small cell lung cancer following progression on or after platinum based chemotherapy. This project aims to explore the synergistic effects and molecular mechanism of TTFields and imipridones in vitro using colorectal and glioblastoma cell lines. Imipridones are a class of anti-cancer drugs that target ClpP and GPCRs and lead to p53 independent apoptosis through chronic activation of the integrated stress response pathway. Both imipridones and TTFields have been shown to inhibit AKT and ERK phosphorylation. Thus, we theorized that co-treatment will have a synergistic effect. We performed ATP-based (Cell Titer Glo) viability assays to determine the IC50 dosage for imipridones ONC201, ONC206 and ONC212 in HT29 and HCT116 colorectal cancer (CRC) cell lines and U251 and T98G glioblastoma (GBM) cell lines. We then treated cells with imipridones at the identified IC50 doses either alone or together with 200kHz TTFields and collected cell lysate after 72 hours. We found differences in AKT phosphorylation across our treatment conditions (control, ONC201, ONC206, ONC212, TTF, TTF + ONC201, TTF + ONC206, and TTF + ONC212). These findings are significant in guiding future in vivo experiments and offering insight on whether TTField and imipridone treatment can be further explored in clinical trials. Citation Format: Viva Voong, Tyler Roady, Connor Purcell, Vida Tajiknia, Lanlan Zhou, Shengliang Zhang, Wafik El-Deiry. Pre-clinical efficacy of tumor treating fields and imipridones in glioblastoma and colorectal cancer cell lines [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 3109.