The Mechanisms of Action of Tumor Treating Fields

Our plain-English summary of The Mechanisms of Action of Tumor Treating Fields, by J.C. Moser, E. Salvador, K. Deniz, et al (Cancer Research, 2022).

The study

• Authors: J.C. Moser, E. Salvador, K. Deniz, K. Swanson, J. Tuszynski, K.W. Carlson, N.K. Karanam, C.B. Patel, M. Story, E. Lou, C. Hagemann
• Journal: Cancer Research
• Published: 2022;82(20):3650-3658
• Type of article: Review
• Cited by: 98 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of action.

©2022 The Authors; Published by the American Association for Cancer Research.

In plain English

This article was a review, not a new study. The authors reviewed published research on tumor treating fields (TTFields): alternating electric fields of 100 to 400 kHz delivered through the skin to tumors, which the FDA has approved for glioblastoma and mesothelioma. The review did not discuss asbestos. It described laboratory and animal findings pointing to several mechanisms, including disrupted cell division, autophagy, DNA replication stress, immune effects, reduced cell migration and increased membrane permeability. For mesothelioma, it reported on the single-arm phase II STELLAR trial. That trial gave TTFields with platinum chemotherapy and pemetrexed to patients with malignant mesothelioma who could not have surgery. Among 80 patients, the overall response rate was 40%, median overall survival was 18.2 months and median progression-free survival was 7.6 months. In a trial in recurrent glioblastoma, the differences favoring TTFields were not statistically significant. Apart from skin irritation, no other significant safety signals were noted. The authors named practical limits: placing the patches and wearing the device 18 hours a day. They concluded that TTFields could be combined with many anticancer therapies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published preclinical (cell and animal) research and clinical trials of tumor treating fields
• Who was studied: No new population was studied. The review covered cancer cell lines, animal models and clinical trials, including the STELLAR trial of 80 patients with malignant mesothelioma who were not candidates for surgical resection
• Exposure: Tumor treating fields, which are alternating electric fields of 100 to 400 kHz delivered through the skin (150 kHz in the mesothelioma trial). The article does not concern asbestos exposure.
• Main results:
  • In the STELLAR trial (malignant mesothelioma, not surgical candidates, TTFields plus a platinum agent and pemetrexed), the overall response rate was 40%, median overall survival was 18.2 months and median progression-free survival was 7.6 months. The trial met its primary endpoint, which was comparison with a median overall survival of 12.1 months reported in a prior phase III trial of platinum agent with pemetrexed.
  • In recurrent glioblastoma, 120 patients received TTFields and 117 received standard chemotherapy. Overall response rate was 14% versus 9.6% and median overall survival was 6.6 versus 6 months. These differences were not statistically significant.
  • In newly diagnosed glioblastoma, an interim analysis of 315 patients showed median overall survival of 19.6 versus 16.6 months for TTFields plus temozolomide versus temozolomide alone. In the final analysis, median progression-free survival was 6.7 versus 4.0 months and median overall survival was 20.9 versus 16.0 months.
  • Laboratory studies reviewed suggested multiple mechanisms, including disruption of cell division, autophagy, DNA replication stress, immune effects, reduced cell migration and increased cancer cell membrane permeability.
  • On safety, grade 1 skin rash occurred in 3 of 6 patients in the initial phase I study. Other than dermatitis, no other significant safety signals were noted in later trials.
• The authors' conclusion: The authors concluded that, given its many mechanisms of action, TTFields have potential to be combined effectively with many types of anticancer therapy for many tumor types.
• Limitations the authors state:
  • The main practical limitations are applying the patches and the time the device must be worn.
  • The patches can be hard to place on some body areas, such as the extremities, which makes studying the therapy in those areas difficult.
  • Use is generally recommended for 18 hours a day, and patients must carry a power supply.
  • It is unknown whether autophagy contributes to the cell-killing effects of TTFields or is a way cells resist it.

Topics

Medical terms in this study, explained in our Lexicon: Tumor Treating Fields (TTFields), Mesothelioma.

Related studies

• Tumour treating fields therapy for glioblastoma: current advances and future directions — O. Rominiyi, A. Vanderlinden, et al. (2021)
• Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook — G.L. Ceresoli, L. Gianoncelli (2025)
• Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel — T. Kan, T. Haj Khalil, et al. (2026)
• Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma — D. Chen, S.B. Le, et al. (2022)
• A review of tumor treating fields (TTFields): advancements in clinical applications and mechanistic insights — X. Li, K. Liu, et al. (2023)
• The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts — N.A. Oberheim-Bush, W. Shi, et al. (2022)

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