Mitotic machinery (Tubulin and Septins) (TTFields target)

The mitotic machinery, primarily comprising alpha/beta-tubulin dimers and septin proteins (SEPT2, SEPT6, SEPT7), serves as the primary therapeutic target for Tumor Treating Fields (TTFields) (Gera et al., 2015). TTFields are low-intensity, intermediate-frequency alternating electric fields that disrupt the assembly of these highly polar proteins during mitosis (Kirson et al., 2007). By interfering with the polymerization of microtubules and the localization of the septin complex, TTFields cause mitotic spindle instability and prevent the formation of the contractile ring during cytokinesis (Mun et al., 2018). This leads to mitotic arrest, chromosomal misalignment, and subsequent cell death via apoptosis or permanent growth arrest in rapidly dividing cancer cells. Clinically, this target is exploited using the Optune device for the treatment of glioblastoma multiforme and malignant pleural mesothelioma, often showing synergy with microtubule-stabilizing drugs like taxanes (Stupp et al., 2017; Rominiyi et al., 2021).

Other names

Mitotic spindleTubulin-septin complexCytoskeletal proteinsTumor Treating Fields target

Disruption of dipole alignment in highly polar proteins (tubulin and septins) via alternating electric fields, leading to mitotic arrest and apoptosis (Kirson et al., 2007; Gera et al., 2015).