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

• Published in: British 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
• Language: English
• 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
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-020-01136-5

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.