Abstract 6891: Tumor treating fields with imipridone ONC206 in murine model of colorectal cancer

Abstract Colorectal Cancer is the third leading cause of cancer-related death in men and the fourth leading cause of cancer-related death in women in the United States. Treatment options include surgery, Chemotherapy, Radiation therapy, and immunotherapy. Despite multiple treatment options, colorectal cancer treatment remains a challenge. Tumor Treating Fields (TTFields) Therapy are FDA-approved for the Treatment of glioblastoma (GBM), Mesothelioma and metastatic NSCLC after platinum-based therapy, and showed preclinical and clinical efficacy in multiple cancer types. TTFields use alternating electric fields to induce cellular damage, suppress tumor growth and activate integrated stress response. Imipridones, TRAIL pathway-inducing compounds, activate the integrated stress response, especially through the eIF2α/ATF4 pathway. We hypothesized that combining TTFields and Imipridone ONC206(DRD2 antagonist and ClpP agonist) can increase treatment efficacy in colorectal cancer through common pathways like integrated stress response. Animal experiments were performed using the inovivo system that allows to treat mice with TTFields, The MC38 cell line was injected into the flanks of C57BL/6 mice, The mice were closely monitored for changes in weight, general appearance, and movement. Treatments were initiated once the tumor volume reached 75-100 mm3 and continued for 12 days. The mice were divided into four groups: sham heat control (N=4), sham heat and ONC206 (100 mg/kg weekly)(N=4), TTFields (N=3) , and TTFields and ONC206 (100 mg/kg weekly)(N=4). We observed a decrease in tumor volume following treatment with ONC206 and Tumor Treating Fields compared to sham heat control with a Pvalue of 0.0233; No significant percentage weight loss was observed in treatment groups. Our ongoing studies further explore the effect of synergy on common pathways. Our results suggest an effective novel combination of Imipridone ONC206 and TTFields for the treatment of colorectal cancer. Citation Format: Leiqing Zhang, Maryam Ghandali, Connor Purcell, Lanlan Zhou, Wafik S. El-Deiry. Tumor treating fields with imipridone ONC206 in murine model of colorectal cancer [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 6891.