Tumor Treating Fields-induced mitotic disruption (TTFields)

Tumor Treating Fields (TTFields) are a non-invasive physical cancer therapy where low-intensity, intermediate-frequency alternating electric fields are delivered locally to tumors via electrode arrays placed on the skin. TTFields primarily act by disrupting mitosis in dividing cancer cells, through mechanisms including interference with mitotic spindle formation, dielectrophoretic movement of polar molecules during cytokinesis, and concentration of the electric field at the cleavage furrow leading to cell fragmentation and apoptosis. TTFields also induce immunogenic cell death, downregulate DNA repair pathways, and impair cytoskeletal dynamics, thereby inhibiting cell migration and metastatic potential. TTFields have FDA approval for use in glioblastoma and mesothelioma, with ongoing studies in other solid tumor types. These fields are most effective due to their selective action on rapidly dividing cells, sparing normal, slow-dividing tissues and producing minimal systemic toxicity; main safety concerns relate to local skin effects.

Other names

TTFields action on mitosisTumor Treating Fields mitotic inhibitionAntimitotic activity of TTFieldsTTF-induced mitotic disruption

Disruption of mitotic spindle assembly via dipole alignment and dielectrophoresis; Arrests cells in metaphase and anaphase; Disorganization of microtubules; Fragmentation of cells during cytokinesis due to field concentration at cleavage furrow; Induction of apoptotic and/or immunogenic cell death (including exposure of calreticulin, release of HMGB1, autophagy-mediated ATP release); Downregulation of DNA damage repair pathways; Disruption of cytoskeleton and cell migration (anti-metastatic effects); Recruitment of immune response and macrophage activation.