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INTERNATIONAL CONGRESS OF

CancerGenetics

• Tumor-treating Fields (TTFields) review article

• Hanieh Askari,¹ Saman Hakimian,^2,*
  1. Biotechnology student , Kashan University
  2. M.sc student of Microbiology Islamic Azad University Central Tehran Branch, Iran, Tehran
  
  
  
• Introduction: Tumor-treating Fields (TTFields), a noninvasive anticancer treatment modality, are low intensity (1–3 V/cm), intermediate frequency(100–300 kHz), alternating electric fields delivered through noninvasive transducer arrays placed locoregionally around the anatomic region of the tumor. TTFields selectively disrupt cell division, and have antimitotic effects in different tumor types which causes reducing tumour growth. electrical forces on cell structure proteins interfered with the chromosome separation during mitosis and induced apoptosis. TTFields can inhibit the mitosis of tumor cells by changing the intracellular electric field, which may effectively overcome chemoradiotherapy resistance. TTFields have been studied for less than two decades.
• Methods: clinical trials have been conducted to assess the efficacy of TTFields treatment in other types of cancer as well. These include non-small cell lung cancer (NSCLC), platinum-resistant ovarian cancer (PROC), pancreatic adenocarcinoma (PAC), malignant pleural mesothelioma (MPM), and hepatocellular carcinoma (HCC). Additionally, clinical trials for TTFields treatment in other cancer types are currently ongoing.
• Results: TTFields exert mitotic inhibition effects on dividing cells through two main aspects. Firstly, the electric field force and torque disrupt the microtubule assembly process during prophase, leading to spindle damage. Secondly, during telophase, the inhomogeneous electric field in the cell generates dielectrophoresis (DEP) force, driving free macromolecules and organelles towards the cleavage furrow, thereby unbalancing the intracellular microenvironment and ultimately causing the death of the dividing cell.
• Conclusion: As mentioned, TTFields interfere with mitosis. TTFields affect mitosis only in actively proliferating tumor cells; normal nerve cells are considered unaffected because they divide slowly. The antimitogenic effect of TTFields is accomplished by electric field force-mediated dipole rearrangement and dielectrophoretic effects. During tumor cell proliferation, α/β tubulin dimers are arranged by their own electric fields to form spindles, and the septin2-6-7 complex is positioned to form a cleavage furrow and contractile ring. TTFields act mainly on these two high-dipole-moment proteins in tumor cells. First, during mitotic metaphase, tubulin is disturbed by uniform alternating electric field forces generated by TTFields. Tubulin oscillates and spins, disrupting the stability of microtubule heterodimeric protein polymerization and leading to spindle assembly errors and abnormal geometric shapes. Eventually, these effects cause delayed mitosis, abnormal mitotic exit in tumor cells, decreased cell proliferation, and aneuploid cell formation. Next, during mitotic anaphase, electric field forces interfere with the movement and binding of the septin protein, inhibiting its midline localization and function. The contractile elements of the cell membrane spread in a disordered manner throughout the cell, which eventually undergoes violent ectopic contraction, causing cell membrane blebbing. Finally, during mitotic telophase, the cell acquires an hourglass shape, and the electric field lines are highly clustered at the cleavage furrow, generating an uneven alternating electric field that exerts a dielectrophoretic effect on the cytoplasm; in this process, charged macromolecules and organelles are propelled toward the neck of the daughter cell that will soon separate. The cell membrane pressure increases, and the cell ruptures and dies.
• Keywords: TTFields, cancer, cancer treatment, tumor-treating fields