Abstract 5569: Tumor Treating Fields inhibit the growth of pancreatic and ovarian cancer in preclinical models .

Abstract

Abstract Tumor Treating Fields (TTFields) therapy is an established anti-mitotic treatment modality. The Novo TTF-100A system, which delivers TTFields to the brain received FDA approval for the treatment of patients with Recurrent Glioblastoma (GBM) Brain Tumors. The goal of the present study is to test whether TTFields therapy is effective as a treatment in pre-clinical models of pancreatic and ovarian cancer. TTFields of various frequencies were applied for 72h to cancerous tumor cells using two pairs of perpendicular insulated electrodes. Pancreatic adenocarcinoma and ovarian carcinoma culture growth was significantly reduced compared to controls (65%+10% and 21%+13%, respectively) with a maximal inhibitory effect seen at 150 and 200 kHz (respectively). The surviving cells exhibited increased cell volume (35%+11% and 61%+43% for pancreatic and ovarian cell lines, respectively) and a reduced viability. Fluorescence microscopy and FACS analysis revealed abnormal mitotic figure in the treated cells cultures and an increase in the 4N population, suggesting these cells failed to complete mitosis. Yet, the increase in the 4N cells fraction was too small to explain for the observed increase in cell volume in the entire remaining cell population. Combining TTFields with gemcitabine and paclitaxel commonly used for the treatment of pancreatic and ovarian cancer, enhanced treatment efficacy and led to a further increase in cell volume. The efficacy of TTFields either alone or in combination with 5FU or gemcitabine was tested in hamsters bearing syngeneic, orthotopic pancreatic tumors. In vivo imaging as well as post mortem analysis demonstrated a significant decrease in tumor weight and volume. Compared to chemotherapy treatment alone, TTF had a sensitizing effect and increased tumor response to chemotherapy. Based on previous reports, the observed increase in cell volume is expected to shift the peak response to TTFields to a lower frequency, allowing some of the cells to escape the effect of TTFields. While this is the first proposed mechanism of resistance to TTFields it also opens the possibility of overcoming that resistance using serial application of several frequencies. Citation Format: Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Mijal Munster, Aviran Itzhaki, Daniel Mordechovich, Shay Cahal, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Tumor Treating Fields inhibit the growth of pancreatic and ovarian cancer in preclinical models . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2013-5569