Tumor Treating Fields in the Management of Patients with Malignant Gliomas

Ghiaseddin, Ashley; Shin, David; Melnick, Kaitlyn; Tran, David

doi:10.1007/s11864-020-00773-5

Cited by 57 publications

(51 citation statements)

References 95 publications

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“…It was approved by the FDA since 2011 for recurrent GBM. Beside antiproliferative and anti-mitotic effects, this device efficacy might also be related to inhibition of migration, invasion, angiogenesis and DNA repair as well as induction of apoptosis and immune effects [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Silva

Mercier

Étienne-Selloum

et al. 2021

Cancers

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Glioblastoma (GBM), the most frequent and aggressive glial tumor, is currently treated as first line by the Stupp protocol, which combines, after surgery, radiotherapy and chemotherapy. For recurrent GBM, in absence of standard treatment or available clinical trials, various protocols including cytotoxic drugs and/or bevacizumab are currently applied. Despite these heavy treatments, the mean overall survival of patients is under 18 months. Many clinical studies are underway. Based on clinicaltrials.org and conducted up to 1 April 2020, this review lists, not only main, but all targeted therapies in phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs for the last twenty years. It does not involve targeted immunotherapies and therapies targeting tumor cell metabolism, that are well documented in other reviews. Without surprise, the most frequently reported drugs are those targeting (i) EGFR (40 clinical trials), and more generally tyrosine kinase receptors (85 clinical trials) and (ii) VEGF/VEGFR (75 clinical trials of which 53 involving bevacizumab). But many other targets and drugs are of interest. They are all listed and thoroughly described, on an one-on-one basis, in four sections related to targeting (i) GBM stem cells and stem cell pathways, (ii) the growth autonomy and migration, (iii) the cell cycle and the escape to cell death, (iv) and angiogenesis.

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Section: Introductionmentioning

confidence: 99%

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Silva

Mercier

Étienne-Selloum

et al. 2021

Cancers

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“…It has been reported previously that TTFields inhibit tumor cell proliferation, [28][29][30] promote apoptosis, [31][32][33] and increase CD8 + T-cell infiltration in the tumor. 14 To determine whether TEFT suppresses glioblastoma growth by similar mechanisms, we performed immunohistochemical staining on tumor specimens (Figure 6A).…”

Section: Teft-r Promotes Apoptosis and Cd8+ T-cell Infiltration In Vivomentioning

confidence: 99%

Exploring the efficacy of tumor electric field therapy against glioblastoma: An in vivo and in vitro study

Yang

Liu

et al. 2021

CNS Neurosci Ther

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AimsTumor electric fields therapy (TTFields) is emerging as a novel anti‐cancer physiotherapy. Despite recent breakthroughs of TTFields in glioma treatment, the average survival time for glioblastoma patients with TTFields is <2 years, even when used in conjugation with traditional anti‐cancer therapies. To optimize TTFields‐afforded efficacy against glioblastoma, we investigated the cancer cell‐killing effects of various TTFields paradigms using in vitro and in vivo models of glioblastoma.MethodsFor in vitro studies, the U251 glioma cell line or primary cell cultures prepared from 20 glioblastoma patients were treated with the tumor electric field treatment (TEFT) system. Cell number, volume, and proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, or 220 kHz), durations (24, 48, or 72 h), field strengths (1.0, 1.5, or 2.2V/cm), and output modes (fixed or random sequence output). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary glioblastoma cells. For in vivo studies, the therapeutic effect and safety profiles of random sequence electric field therapy in glioblastoma‐transplanted rats were assessed by calculating tumor size and survival time and evaluating peripheral immunobiological and blood parameters, respectively.ResultsIn the in vitro settings, TEFT was robustly effective in suppressing cell proliferation of both the U251 glioma cell line and primary glioblastoma cell cultures. The anti‐proliferation effects of TEFT were frequency‐ and “dose” (field strength and duration)‐dependent, and contingent on the field sequence output mode, with the random sequence mode (TEFT‐R) being more effective than the fixed sequence mode (TEFT‐F). Genetic tests were performed in 11 of 20 primary glioblastoma cultures, and 6 different genetic traits were identified them. However, TEFT exhibited comparable anti‐proliferation effects in all primary cultures regardless of their genetic traits. TEFT also inhibited the invasiveness of primary glioblastoma cells in transwell experiments. In the in vivo rat model of glioblastoma brain transplantation, treatment with TEFT‐F or TEFT‐R at frequency of 200 kHz and field strength of 2.2V/cm for 14 days significantly reduced tumor volume by 42.63% (TEFT‐F vs. control, p = 0.0002) and 63.60% (TEFT‐R vs. control, p < 0.0001), and prolonged animal survival time by 30.15% (TEFT‐F vs. control, p = 0.0415) and 69.85% (TEFT‐R vs. control, p = 0.0064), respectively. The tumor‐bearing rats appeared to be well tolerable to TEFT therapies, showing only moderate increases in blood levels of creatine and red blood cells. Adverse skin reactions were common for TEFT‐treated rats; however, skin reactions were curable by local treatment.ConclusionTumor electric field treatment at optimal frequency, strength, and output mode markedly inhibits the cell viability, proliferation, and invasiveness of primary glioblastoma cells in vitro independent of different genetic traits of the cells. Moreover, a random sequence electric field output confers considerable anti‐cancer effects against glioblastoma in vivo. Thus, TTFields are a promising physiotherapy for glioblastoma and warrants further investigation.

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“…It is electromagnetic fields administered through the skin of the scalp and its arrangement is individualized to optimize effect at the tumor site. As it is suggested to target primarily dividing cells during mitosis and causes DNA damage in cycling cells, normal cells in the brain should be spared ( 39 ). Data also suggest that tumor treating fields is both safe and feasible in pediatric patients ( 40 ).…”

Section: Current Treatment Of Brain Tumorsmentioning

confidence: 99%

Targeting MYCN in Molecularly Defined Malignant Brain Tumors

et al. 2021

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Misregulation of MYC genes, causing MYC overexpression or protein stabilization, is frequently found in malignant brain tumors highlighting their important roles as oncogenes. Brain tumors in children are the most lethal of all pediatric malignancies and the most common malignant primary adult brain tumor, glioblastoma, is still practically incurable. MYCN is one of three MYC family members and is crucial for normal brain development. It is associated with poor prognosis in many malignant pediatric brain tumor types and is focally amplified in specific adult brain tumors. Targeting MYCN has proved to be challenging due to its undruggable nature as a transcription factor and for its importance in regulating developmental programs also in healthy cells. In this review, we will discuss efforts made to circumvent the difficulty of targeting MYCN specifically by using direct or indirect measures to treat MYCN-driven brain tumors. We will further consider the mechanism of action of these measures and suggest which molecularly defined brain tumor patients that might benefit from MYCN-directed precision therapies.

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Tumor Treating Fields in the Management of Patients with Malignant Gliomas

Cited by 57 publications

References 95 publications

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Exploring the efficacy of tumor electric field therapy against glioblastoma: An in vivo and in vitro study

Targeting MYCN in Molecularly Defined Malignant Brain Tumors

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