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Review
. 2021 Apr 15;11(4):1069-1086.
eCollection 2021.

Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment

Minjie Wang  1 , Chaocai Zhang  2 , Xuan Wang  1 , Hao Yu  1 , Hemei Zhang  2 , Junnv Xu  3 , Jiannong Zhao  2 , Xiaobing Jiang  1
Affiliations
Review

Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment

Minjie Wang et al. Am J Cancer Res. .

Abstract

Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the unique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.

Keywords: Glioblastoma; basic research; clinical application; cocktail therapy; tumor-treating fields.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Advantages and disadvantages of current clinical therapies for glioblastoma. A. Surgical resection; B. Radiotherapy; C. Chemotherapy; D. Targeted therapy; E. Immunotherapy; F. Tumor-treating fields.
Figure 2
Figure 2
Mechanisms of TTFields. Summary of existing and potential mechanisms that have been discovered and proposed in recent years. A. Generation of cell cycle-specific effects; B. Reduction of cancer cell motility and angiogenesis; C. Increase in cancer cell membrane permeability; D. Increase in blood-brain barrier (BBB) permeability; E. Delay in DNA damage repair; F. Regulation of the anticancer immune response; G. Induction of resistance to TTFields.
Figure 3
Figure 3
Potential application prospects of TTFields. TTFields has the potential to be widely implemented in the latest research technologies. A. Organoid/3D bioprinting models; B. Gene editing; C. Liquid biopsy; D. Single-cell RNA sequencing; E. Nanotechnology.
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References

    1. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21:v1–v100. - PMC - PubMed
    1. Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, Richman AR, Silverbush D, Shaw ML, Hebert CM, Dewitt J, Gritsch S, Perez EM, Gonzalez Castro LN, Lan X, Druck N, Rodman C, Dionne D, Kaplan A, Bertalan MS, Small J, Pelton K, Becker S, Bonal D, Nguyen QD, Servis RL, Fung JM, Mylvaganam R, Mayr L, Gojo J, Haberler C, Geyeregger R, Czech T, Slavc I, Nahed BV, Curry WT, Carter BS, Wakimoto H, Brastianos PK, Batchelor TT, Stemmer-Rachamimov A, Martinez-Lage M, Frosch MP, Stamenkovic I, Riggi N, Rheinbay E, Monje M, Rozenblatt-Rosen O, Cahill DP, Patel AP, Hunter T, Verma IM, Ligon KL, Louis DN, Regev A, Bernstein BE, Tirosh I, Suvà ML. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019;178:835–849. e821. - PMC - PubMed
    1. Couturier CP, Ayyadhury S, Le PU, Nadaf J, Monlong J, Riva G, Allache R, Baig S, Yan X, Bourgey M, Lee C, Wang YCD, Wee Yong V, Guiot MC, Najafabadi H, Misic B, Antel J, Bourque G, Ragoussis J, Petrecca K. Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. Nat Commun. 2020;11:3406. - PMC - PubMed
    1. Abadi B, Ahmadi-Zeidabadi M, Dini L, Vergallo C. Stem cell-based therapy treating glioblastoma multiforme. Hematol Oncol Stem Cell Ther. 2020;14:1–15. - PubMed
    1. Haumann R, Videira JC, Kaspers GJL, van Vuurden DG, Hulleman E. Overview of current drug delivery methods across the blood-brain barrier for the treatment of primary brain tumors. CNS Drugs. 2020;34:1121–1131. - PMC - PubMed

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