Abstract 7591: Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib

Abstract Breast cancer is the most common cancer in women worldwide, and the fifth leading cause of cancer-related deaths globally. Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, is usually treated with surgery, chemotherapy, and radiation. Tumor Treating Fields therapy are FDA-approved for the treatment of glioblastoma (GBM) and malignant pleural mesothelioma (MPM). TT Fields use alternating electric fields to inhibit tumor growth through mitotic disruption, cellular damage, integrated stress response activation, and immune mechanisms and inhibit cell proliferation, induce cell death, and cause cell cycle arrest. TT Fields can induce BRCAness and when combined with PARP inhibition, this combination may result in synthetic lethality. We explored the effect of TTFields on two TNBC cell lines MDA-MB436 (BRCA1-mutant, p53-null) and MDA-MB468 (BRCA1 wild-type, p53-mutant) treated with TTFields (150 kHz) for 24 hours. Western blot analysis showed elevation of p21 independent of p53 mutational status. We examined the combination of PARP inhibitor (Talazoparib) with TTFields in MDA-MB468 cells to determine the effect of the combination in BRCA wild-type cancer cells. Western blot analysis showed p21 upregulation after 24 hours in combination without an increase in p53. p21 acts as a G1-checkpoint protein and loss of p21 expression has been observed in a high percentage of human breast cancer cells. Our results suggest a rational and potentially effective therapy that could be further developed and used for the treatment of breast cancer. Our ongoing studies are exploring potential mechanisms of synergy between PARP inhibitor Talazoparib and TTFields using various TNBC models, and the effect of the combination on cell cycle arrest in cell culture and in vivo. Citation Format: Maryam Ghandali, Praveen Srinivasan, Yutong Xia, Eric T. Wong, Robert W. Sobol, Lanlan zhou, Benedito A. Carneiro, Stephanie L. Graff, Wafik S. El-Deiry. Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7591.