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Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition.

Al's Comment:

 I am a big fan of Optune. It is the most effective approved treatment for gbms,  but it is not good enough by itself. We need to find ways to make it work better.  There are about 16 clinical trials going on now that involve Optune and ways to make it work better.   Any of these trials are worthwhile to try.  Experiments like this are needed to identify candidates for the trials. 

Posted on: 09/14/2018

6. Cell Death Discov. 2018 Jul 16;5:12. doi: 10.1038/s41420-018-0079-9. eCollection 2018.
Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition.
Kessler AF1, Frömbling GE1, Gross F1, Hahn M1, Dzokou W1, Ernestus RI1, Löhr M1, Hagemann C1.
Author information:
1. Department of Neurosurgery, University of Würzburg, Tumorbiology Laboratory, Würzburg, Germany.
Tumor treating fields (TTFields) are approved for glioblastoma (GBM) therapy. TTFields disrupt cell division by inhibiting spindle fiber formation. Spindle assembly checkpoint (SAC) inhibition combined with antimitotic drugs synergistically decreases glioma cell growth in cell culture and mice. We hypothesized that SAC inhibition will increase TTFields efficacy. Human GBM cells (U-87 MG, GaMG) were treated with TTFields (200 kHz, 1.7 V/cm) and/or the SAC inhibitor MPS1-IN-3 (IN-3, 4 µM). Cells were counted after 24, 48, and 72 h of treatment and at 24 and 72 h after end of treatment (EOT). Flow cytometry, immunofluorescence microscopy, Annexin-V staining and TUNEL assay were used to detect alterations in cell cycle and apoptosis after 72 h of treatment. The TTFields/IN-3 combination decreased cell proliferation after 72 h compared to either treatment alone (-78.6% vs. TTFields, P = 0.0337; -52.6% vs. IN-3, P = 0.0205), and reduced the number of viable cells (62% less than seeded). There was a significant cell cycle shift from G1 to G2/M phase (P < 0.0001). The apoptotic rate increased to 44% (TTFields 14%, P = 0.0002; IN-3 4%, P < 0.0001). Cell growth recovered 24 h after EOT with TTFields and IN-3 alone, but the combination led to further decrease by 92% at 72 h EOT if IN-3 treatment was continued (P = 0.0288). The combination of TTFields and SAC inhibition led to earlier and prolonged effects that significantly augmented the efficacy of TTFields and highlights a potential new targeted multimodal treatment for GBM.
PMCID: PMC6125382
PMID: 30210815
Conflict of interest statemen


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