A Theoretical Study on the Biophysical Mechanisms by Which Tumor Treating Fields Affect Tumor Cells During Mitosis

Objective: A theoretical study on the mechanisms through which Tumor Treating Fields (TTFields) affect dividing tumor cells. Methods: Numerical analysis was used to revisit two previously proposed mechanisms and introduce a third. We examine the previous hypotheses that: a) TTFields generate a moment that affects microtubule assembly during early mitosis, and b) dielectrophoretic (DEP) forces cause neutral particles to move toward the cleavage furrow during the telophase stage. We further introduce a new hypothesis that TTFields modify cell membrane potential in dividing tumor cells. Results: a) The Brownian energy is several orders of magnitude larger than the moment induced by TTFields on tubulin dimers. b) Adding Stokes drag forces to DEP forces shows that the motion of the particles in the cytoplasm is very slow, approximately 0.003 μm/s, and therefore, unless the duration of the telophase is long enough there will be no substantial effect from the DEP forces. c) The Schwan equation shows that electric fields at the frequencies of clinical TTFields can cause a 10%-17% change in tumor cell membrane potential. Conclusion: Our studies find limited support for the previously suggested hypotheses and suggest that the TTFields affect ion channels by inducing cell membrane potential change could be a mechanism of tumor cell death. Significance: Previously suggested mechanisms of tumor cell death from TTFields are found lacking. The effect of TTFields on the tumor cell membrane potential warrants further research.