Abstract 307: The combined treatment of 150 kHz Tumor Treating Fields (TTFields) and Cisplatin or Pemetrexed inhibit mesothelioma cells in vitro
Authors: Munster Mijal , Schneiderman Rosa , Porat Yaara , Voloshin Tali , Davidi Shiri , Shteingauz Anna , Kaynan Noa , Zeevi Einav , Gotlib Karnit , Giladi Moshe , Kirson Eilon , Weinberg Uri , Kinzel Adrian , Palti Yoram 
Published: August 2019

Abstract
Malignant pleural mesothelioma (MPM) is a rare thoracic solid tumor cancer that has been strongly linked to asbestos exposure. The standard of care treatment for unresectable mesothelioma is cisplatin plus pemetrexed chemotherapy which offer short and insufficient efficacy. Furthermore, no validated treatment beyond first-line therapy is available. Thus, there is an urgent need to identify more effective treatments for mesothelioma patients. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. TTFields are employed as a local treatment with the intent to target dividing cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation and the induction of different forms of cancer cell death. The aim of this work is to explore the potential of the use of TTFields alone and in combination with cisplatin or pemetrexed as a treatment for Mesothelioma. MSTO-211H and NCI-H2052 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Cisplatin or Pemetrexed was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, and clonogenic potential were determined at the end of treatment. The optimal TTFields frequency leading to the highest reduction in cell counts was found to be 150 kHz for both MSTO-211H and NCI-H2052 cells. TTFields application (1.1 V/cm, 72 hours) at 150 kHz led to 51%, 65% reduction in cell counts, 40%, 55% reduction in the clonogenic potential in NCI-H2052 and MSTO-211H cells, respectively. The combined treatment of TTFields and Cisplatin or Pemetrexed led to a significant reduction in cell count, induction of apoptosis and reduced clonogenic potential as compared to each modality alone. (2-way ANOVA, p&lt0.0001). Safety studies did not reveal any adverse event associated with 150 kHz TTFields application to the rat torso. The results presented in this work demonstrate that TTFields can be an effective treatment against Mesothelioma cells and that the combination with cisplatin or pemetrexed may further enhance treatment efficacy. In accordance with these results, it was recently reported that patients treated by the combined treatment of TTFields with pemetrexed and cisplatin experienced improved overall survival as compared to historical control with no increase in systemic toxicity.
Citation Format: Mijal Munster, Rosa Schneiderman, Yaara Porat, Tali Voloshin, Shiri Davidi, Anna Shteingauz, Noa Kaynan, Einav Zeevi, Karnit Gotlib, Moshe Giladi, Eilon Kirson, Uri Weinberg, Adrian Kinzel, Yoram Palti. The combined treatment of 150 kHz Tumor Treating Fields (TTFields) and Cisplatin or Pemetrexed inhibit mesothelioma cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 307.