The schemes, mechanisms and molecular pathway changes of Tumor Treating Fields (TTFields) alone or in combination with radiotherapy and chemotherapy.

in Cell death discovery by Guilong Tanzhu, Liu Chen, Gang Xiao, Wen Shi, Haiqin Peng, Dikang Chen, Rongrong Zhou

TLDR

  • TTFields is a physical therapy that inhibits tumor growth by affecting tumor cell proliferation, invasion, and migration, and regulates immune function and cellular processes.
  • The study reviews the in-vitro effects of TTFields and its potential combination with radiotherapy and chemotherapy.

Abstract

Tumor Treating Fields (TTFields) is a physical therapy that uses moderate frequency (100-300 kHz) and low-intensity (1-3 V/cm) alternating electric fields to inhibit tumors. Currently, the Food and Drug Administration approves TTFields for treating recurrent or newly diagnosed glioblastoma (GBM) and malignant pleural mesothelioma (MPM). The classical mechanism of TTFields is mitotic inhibition by hindering the formation of tubulin and spindle. In addition, TTFields inhibits cell proliferation, invasion, migration and induces cell death, such as apoptosis, autophagy, pyroptosis, and cell cycle arrest. Meanwhile, it regulates immune function and changes the permeability of the nuclear membrane, cell membrane, and blood-brain barrier. Based on the current researches on TTFields in various tumors, this review comprehensively summarizes the in-vitro effects, changes in pathways and molecules corresponding to relevant parameters of TTFields (frequency, intensity, and duration). In addition, radiotherapy and chemotherapy are common tumor treatments. Thus, we also pay attention to the sequence and dose when TTFields combined with radiotherapy or chemotherapy. TTFields has inhibitory effects in a variety of tumors. The study of TTFields mechanism is conducive to subsequent research. How to combine common tumor therapy such as radiotherapy and chemotherapy to obtain the maximum benefit is also a problem that's worthy of our attention.

Overview

  • The study reviews the in-vitro effects of Tumor Treating Fields (TTFields) on various tumors, focusing on the mechanisms of action, changes in pathways and molecules, and combination therapy with radiotherapy and chemotherapy.
  • TTFields is a physical therapy that uses moderate frequency (100-300 kHz) and low-intensity (1-3 V/cm) alternating electric fields to inhibit tumors.
  • The main objectives of the study are to summarize the effects of TTFields, explore its mechanisms of action, and investigate the combination of TTFields with other tumor treatments.

Comparative Analysis & Findings

  • TTFields inhibits tumor growth by mitotic inhibition, cell proliferation, invasion, migration, and induces cell death, such as apoptosis, autophagy, pyroptosis, and cell cycle arrest.
  • TTFields regulates immune function and changes the permeability of the nuclear membrane, cell membrane, and blood-brain barrier.
  • There is no significant difference in the effect of TTFields on different tumors, but more studies are needed to confirm this.

Implications and Future Directions

  • The study highlights the significance of TTFields in combating various tumors and its potential as a new tumor treatment option.
  • The study suggests that combining TTFields with radiotherapy and chemotherapy may enhance treatment efficacy and reduce side effects.
  • Future studies should focus on the optimized combination of TTFields with other tumor treatments and its long-term safety and efficacy in humans.
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