Tubulin and Septins (TTFields targets) (TTFields)

Tumor Treating Fields (TTFields) are a non-invasive cancer therapy that utilizes intermediate-frequency alternating electric fields to disrupt the division of malignant cells. The primary molecular targets of TTFields are highly polar cytoskeletal proteins, specifically tubulin dimers and septin complexes (Septin 2, 6, and 7), which possess significant intrinsic dipole moments [1][2]. By exerting dielectrophoretic forces on these dipoles, TTFields interfere with the proper assembly of the mitotic spindle and the localization of the cytokinetic cleavage furrow [3]. This disruption leads to mitotic arrest, cell death, and the inhibition of cell motility and invasion by preventing the dynamic reorganization of the cytoskeleton required for migration [4]. Clinically, TTFields are delivered via the Optune device and are approved for treating glioblastoma multiforme and malignant pleural mesothelioma [5]. The therapy is frequently combined with chemotherapy, such as temozolomide, to enhance anti-tumor efficacy while maintaining a safety profile primarily limited to local skin reactions [6]. Sources: [1] Kirson ED, et al. (2007). PNAS. [2] Voloshin T, et al. (2016). Cancer Research. [3] Gera N, et al. (2015). PLOS ONE. [4] Giladi M, et al. (2015). Scientific Reports. [5] Stupp R, et al. (2017). JAMA. [6] Novocure Ltd. (2024). Optune Instructions for Use.

Other names

Alternating electric fieldsTTFMicrotubule and septin disruptionOptune mechanismIntermediate-frequency alternating electric fields

TTFields exert dielectrophoretic forces on highly polar molecules like tubulin and septins, preventing their proper alignment and polymerization during mitosis and cell migration.