Article Text
Abstract
Introduction/Background Tumor Treating Fields (TTFields) therapy is a clinically active anticancer modality which utilizes alternating electric fields with low intensity and intermediate frequency. A recent study, which investigated the effects of TTFields concomitantly with paclitaxel on ovarian cancer, showed a significant reduction in ovarian cancer cell growth in vitro. For many years IGF1R signaling has been implicated as a critical contributor to cancer cell proliferation, survival, and migration, and therefore was identified as a potential therapeutic target in different types of cancer including epithelial ovarian cancer (EOC). Considering the promising approach of combination treatment, we hypothesize that the addition of IGF1R targeted therapy to TTFields treatment might improve the effect on ovarian cancer.
Methodology To investigate the effect of TTFields treatment and IGF1R targeting co application on ovarian cancer cells, human EOC cell lines Caov-3 and OVCAR3 were treated with TTFields and AEW, a selective IGF1R inhibitor, using a concentration of 3 µM and 5 µM respectively, for 72 hr. TTFields were applied using the inovitro™ system (Novocure, Israel) at an intensity of 1.75 V/cm (RMS) and a frequency of 200 kHz. Inhibition of cell growth was analyzed by determining cell count using flow cytometry.
Results Application of TTFields with AEW treatment in OVCAR3 cells resulted in a 62% reduction in cell count as compared to control (P<0.01), while TTFields and AEW single treatments resulted in a 24% and 37% reduction in cell count, respectively, compared to the control. Similar results were observed in Caov-3 cells (61%, 33%, 31% respectively, P<0.01).
Conclusion IGF1R pathway inhibition with TTFields treatment in epithelial ovarian cancer cells resulted in an additive inhibitory effect on cell growth. We believe that implementation of these treatment strategy might have significant clinical ramifications.
Disclosures The authors have no conflict of interest to declare.
This research was conducted in collaboration with Novocure Israel Ltd.