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Keywords = Optune®

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21 pages, 952 KiB  
Review
Tumor Treating Fields and Combination Therapy in Management of Brain Oncology
by Ruisi Nicole Liu, James H. Huang, Xiaoming Qi, Yizhong Pan, Erxi Wu and Damir Nizamutdinov
Cancers 2025, 17(7), 1211; https://doi.org/10.3390/cancers17071211 - 2 Apr 2025
Viewed by 1876
Abstract
Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; [...] Read more.
Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance and lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), a novel non-invasive modality that utilizes alternating electric fields, have recently emerged as a promising treatment for GBM. TTFields work by disrupting the function of the mitotic spindle and inducing apoptosis in cancer cells. They can be especially effective when combined with other therapies. TTFields enhance drug delivery when paired with chemotherapy by increasing the permeability of the blood–brain barrier and cell membranes, leading to more effective tumor inhibition. Similarly, TTFields increase cancer cell sensitivity to radiation therapy and improve the efficacy of targeted therapies, such as sorafenib and immunotherapy, particularly in extra-cranial tumors. The Optune device, the primary medical device for TTFields’ delivery, offers a convenient and versatile treatment option, allowing remote care and exhibiting fewer adverse effects. This review discusses the potential of TTFields as a valuable addition to GBM treatment, particularly in combination therapies, and highlights the device’s clinical applications. Full article
(This article belongs to the Special Issue Combination Therapies for Brain Tumors)
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6 pages, 5060 KiB  
Brief Report
First Report of Tumor Treating Fields (TTFields) Therapy for Glioblastoma in Comorbidity with Multiple Sclerosis
by Rebecca Kassubek and René Mathieu
Brain Sci. 2022, 12(4), 499; https://doi.org/10.3390/brainsci12040499 - 13 Apr 2022
Cited by 3 | Viewed by 2942
Abstract
Tumor Treating Fields (TTFields) therapy is FDA approved and has the CE mark for treatment of newly diagnosed and recurrent glioblastoma. To our knowledge, to date TTFields therapy remains unstudied in glioblastoma patients with multiple sclerosis (MS) as a comorbidity. Here, we present [...] Read more.
Tumor Treating Fields (TTFields) therapy is FDA approved and has the CE mark for treatment of newly diagnosed and recurrent glioblastoma. To our knowledge, to date TTFields therapy remains unstudied in glioblastoma patients with multiple sclerosis (MS) as a comorbidity. Here, we present a patient who was diagnosed with MS at the age of 34. Treatment included several corticoid pulse treatments and therapies with interferon beta-1a and sphingosine-1-phosphate receptor modulator fingolimod. At the age of 52 the patient was diagnosed with glioblastoma, after experiencing worsening headaches which could not be attributed to the MS condition. After subtotal resection and concomitant radiochemotherapy, the patient received temozolomide in combination with TTFields therapy. For two years, the tumor condition remained stable while the patient showed high adherence to TTFields therapy with low-grade skin reactions being the only therapy-related adverse events. After two years, the tumor recurred. The patient underwent re-resection and radiotherapy and restarted TTFields therapy together with chemotherapy and is currently still on this therapy regime. Although having not been studied systematically, the case presented here demonstrates that TTFields therapy may be considered for newly diagnosed and recurrent glioblastoma patients with previously diagnosed multiple sclerosis. Full article
(This article belongs to the Section Neuro-oncology)
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18 pages, 2683 KiB  
Article
Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors
by Joshua Branter, Maria Estevez-Cebrero, Mohammed Diksin, Michaela Griffin, Marcos Castellanos-Uribe, Sean May, Ruman Rahman, Richard Grundy, Surajit Basu and Stuart Smith
Int. J. Mol. Sci. 2022, 23(4), 1982; https://doi.org/10.3390/ijms23041982 - 11 Feb 2022
Cited by 14 | Viewed by 3609
Abstract
The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to the [...] Read more.
The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study. Full article
(This article belongs to the Special Issue Frontiers in Neuro-Oncology)
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11 pages, 748 KiB  
Review
Antitumor Activity of Curcumin in Glioblastoma
by Blake C. Walker and Sandeep Mittal
Int. J. Mol. Sci. 2020, 21(24), 9435; https://doi.org/10.3390/ijms21249435 - 11 Dec 2020
Cited by 47 | Viewed by 6067
Abstract
Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® [...] Read more.
Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas. Full article
(This article belongs to the Special Issue Natural Products and Neuroprotection 2.0)
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12 pages, 236 KiB  
Review
Treatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review
by Denise Fabian, Maria del Pilar Guillermo Prieto Eibl, Iyad Alnahhas, Nikhil Sebastian, Pierre Giglio, Vinay Puduvalli, Javier Gonzalez and Joshua D. Palmer
Cancers 2019, 11(2), 174; https://doi.org/10.3390/cancers11020174 - 2 Feb 2019
Cited by 187 | Viewed by 18360
Abstract
Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment, GBM almost always recurs. The current standard-of-care for treatment of newly diagnosed GBM has remained relatively unchanged since 2005: maximal safe resection followed by concomitant chemoradiation (CRT) with temozolomide (TMZ), and [...] Read more.
Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment, GBM almost always recurs. The current standard-of-care for treatment of newly diagnosed GBM has remained relatively unchanged since 2005: maximal safe resection followed by concomitant chemoradiation (CRT) with temozolomide (TMZ), and subsequent adjuvant TMZ. In 2011, the first-generation tumor treating fields (TTF) device, known at the time as the NovoTTF-100A System (renamed Optune), was approved by the Food and Drug Administration (FDA) for treatment of recurrent GBM. The TTF device was subsequently approved as an adjuvant therapy for newly-diagnosed GBM in 2015. The following is a review of the TTF device, including evidence supporting its use and limitations. Full article
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
14 pages, 765 KiB  
Review
Therapeutic Immunization against Glioblastoma
by Virgil E. J. C. Schijns, Chrystel Pretto, Anna M. Strik, Rianne Gloudemans-Rijkers, Laurent Devillers, Denis Pierre, Jinah Chung, Manisha Dandekar, Jose A. Carrillo, Xiao-Tang Kong, Beverly D. Fu, Frank P. K. Hsu, Florence M. Hofman, Thomas C. Chen, Raphael Zidovetzki, Daniela A. Bota and Apostolos Stathopoulos
Int. J. Mol. Sci. 2018, 19(9), 2540; https://doi.org/10.3390/ijms19092540 - 27 Aug 2018
Cited by 15 | Viewed by 6594
Abstract
Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, [...] Read more.
Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation. Full article
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