Mitotic spindle and septin proteins (TTFields target) (TTFields)

Tumor Treating Fields (TTFields) target the mitotic machinery of rapidly dividing cancer cells by utilizing low-intensity, intermediate-frequency alternating electric fields (100–500 kHz) [PMID: 30107315]. The primary molecular targets are highly polar proteins, specifically alpha/beta-tubulin dimers and septin complexes (Septin 2, 6, 7, and 11), which are essential for spindle formation and cytokinesis [PMID: 24864000]. During metaphase, TTFields interfere with the alignment of tubulin dimers, preventing the proper assembly of the mitotic spindle [PMID: 15150577]. During cytokinesis, the fields exert dielectrophoretic forces on septins, causing them to mislocalize and leading to the collapse of the cleavage furrow [PMID: 24864000]. This disruption results in mitotic catastrophe, abnormal chromosome segregation, and subsequent apoptosis or permanent cell cycle arrest [PMID: 28253114]. Clinically, TTFields are delivered via a non-invasive medical device (Optune) and are primarily used to treat glioblastoma and mesothelioma, often in combination with chemotherapy [FDA.gov]. The therapy is unique in that it exploits the physical properties of cellular components rather than their chemical binding sites.

Other names

Tumor Treating FieldsAlternating electric fieldsMitotic machinerySeptin-tubulin complexMitotic spindle

Disruption of mitotic spindle assembly and cytokinesis through dielectrophoretic forces exerted on highly polar molecules, specifically tubulin dimers and septin complexes, leading to mitotic arrest and cell death [PMID: 24864000].