Tumour treating fields therapy for glioblastoma: current advances and future directions

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophys...

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Published inBritish journal of cancer Vol. 124; no. 4; pp. 697 - 709
Main Authors Rominiyi, Ola, Vanderlinden, Aurelie, Clenton, Susan Jane, Bridgewater, Caroline, Al-Tamimi, Yahia, Collis, Spencer James
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.02.2021
Nature Publishing Group
Subjects
631/67/1922
639/766
692/4028/67/1059/485
692/4028/67/1059/602
692/4028/67/1059/99
Animals
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Brain tumors
Cancer
Cancer Research
Cell permeability
Cell proliferation
Chemoradiotherapy
Chemotherapy
Clinical trials
Clinical Trials, Phase III as Topic
DNA repair
Drug Resistance
Electric fields
Electric Stimulation Therapy - methods
Epidemiology
Glioblastoma
Glioblastoma - pathology
Glioblastoma - therapy
Humans
Mesothelioma
Molecular Medicine
Oncology
Radiation therapy
Randomized Controlled Trials as Topic
Review
Review Article
Surgery
Online AccessGet full text

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Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
AbstractList Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
Author Rominiyi, Ola
Clenton, Susan Jane
Bridgewater, Caroline
Collis, Spencer James
Vanderlinden, Aurelie
Al-Tamimi, Yahia
Author_xml – sequence: 1
  givenname: Ola
  orcidid: 0000-0002-9724-0224
  surname: Rominiyi
  fullname: Rominiyi, Ola
  email: o.rominiyi@sheffield.ac.uk
  organization: Weston Park Cancer Centre, Department of Oncology & Metabolism, The University of Sheffield Medical School, Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
– sequence: 2
  givenname: Aurelie
  surname: Vanderlinden
  fullname: Vanderlinden, Aurelie
  organization: Weston Park Cancer Centre, Department of Oncology & Metabolism, The University of Sheffield Medical School
– sequence: 3
  givenname: Susan Jane
  surname: Clenton
  fullname: Clenton, Susan Jane
  organization: Department of Clinical Oncology, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
– sequence: 4
  givenname: Caroline
  surname: Bridgewater
  fullname: Bridgewater, Caroline
  organization: Department of Clinical Oncology, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
– sequence: 5
  givenname: Yahia
  orcidid: 0000-0002-9014-2728
  surname: Al-Tamimi
  fullname: Al-Tamimi, Yahia
  organization: Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
– sequence: 6
  givenname: Spencer James
  orcidid: 0000-0002-7874-1891
  surname: Collis
  fullname: Collis, Spencer James
  email: s.collis@sheffield.ac.uk
  organization: Weston Park Cancer Centre, Department of Oncology & Metabolism, The University of Sheffield Medical School
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33144698$$D View this record in MEDLINE/PubMed
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34112950 - Br J Cancer. 2021 Aug;125(4):623. doi: 10.1038/s41416-021-01451-5.
34316021 - Br J Cancer. 2021 Sep;125(6):901-903. doi: 10.1038/s41416-021-01504-9.
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Snippet Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using...
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639/766
692/4028/67/1059/485
692/4028/67/1059/602
692/4028/67/1059/99
Animals
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Brain tumors
Cancer
Cancer Research
Cell permeability
Cell proliferation
Chemoradiotherapy
Chemotherapy
Clinical trials
Clinical Trials, Phase III as Topic
DNA repair
Drug Resistance
Electric fields
Electric Stimulation Therapy - methods
Epidemiology
Glioblastoma
Glioblastoma - pathology
Glioblastoma - therapy
Humans
Mesothelioma
Molecular Medicine
Oncology
Radiation therapy
Randomized Controlled Trials as Topic
Review
Review Article
Surgery
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Title Tumour treating fields therapy for glioblastoma: current advances and future directions
URI https://link.springer.com/article/10.1038/s41416-020-01136-5
https://www.ncbi.nlm.nih.gov/pubmed/33144698
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https://pubmed.ncbi.nlm.nih.gov/PMC7884384
Volume 124
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