Advances in the study of the role of tumor treating fields therapy in the treatment of glioblastoma

doi:10.3760/cma.j.cn371439-20240407-00107

Abstract

Abstract:

Glioblastoma （GBM） is one of the most threatening diseases of the central nervous system， and the prognosis has not improved despite the constant updating of therapeutic approaches. However， the introduction of tumor treating fields （TTFields） has changed the treatment of newly diagnosed and recurrent GBM. TTFields is a novel non-invasive therapy for the treatment of tumors using mid-frequency and low-intensity alternating electric fields， which is important for the treatment of central nervous system diseases such as GBM. TTFields has fewer side effects and greater local efficacy than traditional treatment modalities. In addition， the combination of chemotherapeutic drugs and radiotherapy with TTFields has shown significant advantages and may become one of the future clinical treatment strategies. Despite the potential of TTFields in the treatment of GBM， a number of limitations remain， including issues of device dependency， discomfort during use and tolerability in some patients. Therefore， the use of TTFields needs to be further optimized to maximize their therapeutic potential in patients with GBM and to provide more effective treatment options for patients.

Key words: Glioblastoma, Glioma, Tumor treating fields, Mechanism

Du Aichao, Cheng Houxiang, Dai Junqiang, Pan Yawen. Advances in the study of the role of tumor treating fields therapy in the treatment of glioblastoma[J]. Journal of International Oncology, 2024, 51(10): 639-644.

References 43

[1]	Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016[J]. Neuro Oncol, 2019, 21(Suppl 5): v1-v100. DOI: 10.1093/neuonc/noz150.
[2]	Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary[J]. Neuro Oncol, 2021, 23(8): 1231-1251. DOI: 10.1093/neuonc/noab106.
[3]	肖楠, 孙鹏飞. 氧化应激在胶质瘤放化疗敏感性中的研究进展[J]. 国际肿瘤学杂志, 2022, 49(6): 357-361. DOI: 10.3760/cma.j.cn371439-20220309-00068.
[4]	Xu C, Xiao M, Li X, et al. Origin, activation, and targeted therapy of glioma-associated macrophages[J]. Front Immunol, 2022, 13: 974996. DOI: 10.3389/fimmu.2022.974996.
[5]	Rominiyi O, Vanderlinden A, Clenton SJ, et al. Tumour treating fields therapy for glioblastoma: current advances and future directions[J]. Br J Cancer, 2021, 124(4): 697-709. DOI: 10.1038/s41416-020-01136-5.
[6]	连海伟, 杨烁锐, 刘仁忠. 金松双黄酮联合CX-4945通过Notch1通路调控胶质母细胞瘤细胞增殖与凋亡的机制研究[J]. 国际肿瘤学杂志, 2022, 49(6): 321-326. DOI: 10.3760/cma.j.cn371439-20220118-00061.
[7]	Velásquez C, Mansouri S, Mora C, et al. Molecular and clinical insights into the invasive capacity of glioblastoma cells[J]. J Oncol, 2019, 2019: 1740763. DOI: 10.1155/2019/1740763.
[8]	Shams S, Patel CB. Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields])[J]. J Mol Cell Biol, 2022, 14(8): mjac047. DOI: 10.1093/jmcb/mjac047.
[9]	Barsheshet Y, Voloshin T, Brant B, et al. Tumor treating fields (TTFields) concomitant with immune checkpoint inhibitors are therapeutically effective in non-small cell lung cancer (NSCLC) in vivo model[J]. Int J Mol Sci, 2022, 23(22): 14073. DOI: 10.3390/ijms232214073.
[10]	Ceresoli GL, Aerts JG, Dziadziuszko R, et al. Tumour treating fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial[J]. Lancet Oncol, 2019, 20(12): 1702-1709. DOI: 10.1016/s1470-2045(19)30532-7. pmid: 31628016
[11]	Guo X, Yang X, Wu J, et al. Tumor-treating fields in glioblastomas: past, present, and future[J]. Cancers (Basel), 2022, 14(15): 3669. DOI: 10.3390/cancers14153669.
[12]	Hadjipanayis CG, Stummer W. 5-ALA and FDA approval for glioma surgery[J]. J Neurooncol, 2019, 141(3): 479-486. DOI: 10.1007/s11060-019-03098-y.
[13]	Moser JC, Salvador E, Deniz K, et al. The mechanisms of action of tumor treating fields[J]. Cancer Res, 2022, 82(20): 3650-3658. DOI: 10.1158/0008-5472.Can-22-0887. pmid: 35839284
[14]	Giladi M, Schneiderman RS, Voloshin T, et al. Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells[J]. Sci Rep, 2015, 5: 18046. DOI: 10.1038/srep18046. pmid: 26658786
[15]	Hong P, Kudulaiti N, Wu S, et al. Tumor treating fields: a comprehensive overview of the underlying molecular mechanism[J]. Expert Rev Mol Diagn, 2022, 22(1): 19-28. DOI: 10.1080/14737159.2022.2017283.
[16]	Tanzhu G, Chen L, Xiao G, et al. The schemes, mechanisms and molecular pathway changes of tumor treating fields (TTFields) alone or in combination with radiotherapy and chemotherapy[J]. Cell Death Discov, 2022, 8(1): 416. DOI: 10.1038/s41420-022-01206-y. pmid: 36220835
[17]	Kim EH, Jo Y, Sai S, et al. Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells[J]. Oncogene, 2019, 38(39): 6630-6646. DOI: 10.1038/s41388-019-0882-7. pmid: 31375748
[18]	Belyaeva E, Kharwar RK, Ulasov IV, et al. Isoforms of autophagy-related proteins: role in glioma progression and therapy resistance[J]. Mol Cell Biochem, 2022, 477(2): 593-604. DOI: 10.1007/s11010-021-04308-w.
[19]	Xu S, Luo C, Chen D, et al. Whole transcriptome and proteome analyses identify potential targets and mechanisms underlying tumor treating fields against glioblastoma[J]. Cell Death Dis, 2022, 13(8): 721. DOI: 10.1038/s41419-022-05127-7. pmid: 35982032
[20]	Aguilar AA, Ho MC, Chang E, et al. Permeabilizing cell membranes with electric fields[J]. Cancers (Basel), 2021, 13(9): 2283. DOI: 10.3390/cancers13092283.
[21]	Chang E, Patel CB, Pohling C, et al. Tumor treating fields increases membrane permeability in glioblastoma cells[J]. Cell Death Discovery, 2018, 4(1): 113. DOI: 10.1038/s41420-018-0130-x.
[22]	Salvador E, Kessler AF, Domröse D, et al. Tumor treating fields (TTFields) reversibly permeabilize the blood-brain barrier in vitro and in vivo[J]. Biomolecules, 2022, 12(10): 1348. DOI: 10.3390/biom12101348.
[23]	Li X, Yang F, Rubinsky B. A theoretical study on the biophysical mechanisms by which tumor treating fields affect tumor cells during mitosis[J]. IEEE Trans Biomed Eng, 2020, 67(9): 2594-2602. DOI: 10.1109/tbme.2020.2965883. pmid: 31940516
[24]	Lee WS, Seo SJ, Chung HK, et al. Tumor-treating fields as a proton beam-sensitizer for glioblastoma therapy[J]. Am J Cancer Res, 2021, 11(9): 4582-4594. pmid: 34659907
[25]	Voloshin T, Schneiderman RS, Volodin A, et al. Tumor treating fields (TTFields) hinder cancer cell motility through regulation of microtubule and acting dynamics[J]. Cancers (Basel), 2020, 12(10): 3016. DOI: 10.3390/cancers12103016.
[26]	Prager BC, Bhargava S, Mahadev V, et al. Glioblastoma stem cells: driving resilience through chaos[J]. Trends Cancer, 2020, 6(3): 223-235. DOI: 10.1016/j.trecan.2020.01.009. pmid: 32101725
[27]	Sampson JH, Gunn MD, Fecci PE, et al. Brain immunology and immunotherapy in brain tumours[J]. Nat Rev Cancer, 2020, 20(1): 12-25. DOI: 10.1038/s41568-019-0224-7. pmid: 31806885
[28]	Voloshin T, Kaynan N, Davidi S, et al. Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy[J]. Cancer Immunol Immunother, 2020, 69(7): 1191-1204. DOI: 10.1007/s00262-020-02534-7. pmid: 32144446
[29]	Chen DJ, Le SB, Hutchinson TE, et al. Tumor treating fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma[J]. J Clin Invest, 2022, 132(8): e149258. DOI: 10.1172/jci149258.
[30]	Diamant G, Simchony Goldman H, Gasri Plotnitsky L, et al. T cells retain pivotal antitumoral functions under tumor-treating electric fields[J]. J Immunol, 2021, 207(2): 709-719. DOI: 10.4049/jimmunol.2100100. pmid: 34215656
[31]	Karanam NK, Ding LH, Aroumougame A, et al. Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: implications for cancer therapy[J]. Transl Res, 2020, 217: 33-46. DOI: 10.1016/j.trsl.2019.10.003. pmid: 31707040
[32]	Kim EH, Kim YH, Song HS, et al. Biological effect of an alter-nating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation[J]. Oncotarget, 2016, 7(38): 62267-62279. DOI: 10.18632/oncotarget.11407.
[33]	Giladi M, Munster M, Schneiderman RS, et al. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells[J]. Radiat Oncol, 2017, 12(1): 206. DOI: 10.1186/s13014-017-0941-6. pmid: 29284495
[34]	Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial[J]. JAMA, 2017, 318(23): 2306-2316. DOI: 10.1001/jama.2017.18718. pmid: 29260225
[35]	Guberina N, Pöttgen C, Kebir S, et al. Combined radiotherapy and concurrent tumor treating fields (TTFields) for glioblastoma: dosimetric consequences on non-coplanar IMRT as initial results from a phase Ⅰ trial[J]. Radiat Oncol, 2020, 15(1): 83. DOI: 10.1186/s13014-020-01521-7. pmid: 32307022
[36]	Jo Y, Kim EH, Sai S, et al. Functional biological activity of sorafenib as a tumor-treating field sensitizer for glioblastoma therapy[J]. Int J Mol Sci, 2018, 19(11): 3684. DOI: 10.3390/ijms19113684.
[37]	Kim JY, Jo Y, Oh HK, et al. Sorafenib increases tumor treating fields-induced cell death in glioblastoma by inhibiting STAT3[J]. Am J Cancer Res, 2020, 10(10): 3475-3486.
[38]	Dubinski D, Hattingen E, Senft C, et al. Controversial roles for dexamethasone in glioblastoma—opportunities for novel vascular targeting therapies[J]. J Cereb Blood Flow Metab, 2019, 39(8): 1460-1468. DOI: 10.1177/0271678x19859847.
[39]	Iorgulescu JB, Gokhale PC, Speranza MC, et al. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma[J]. Clin Cancer Res, 2021, 27(1): 276-287. DOI: 10.1158/1078-0432.Ccr-20-2291. pmid: 33239433
[40]	Linder B, Schiesl A, Voss M, et al. Dexamethasone treatment limits efficacy of radiation, but does not interfere with glioma cell death induced by tumor treating fields[J]. Front Oncol, 2021, 11: 715031. DOI: 10.3389/fonc.2021.715031.
[41]	Shi WY, Blumenthal DT, Oberheim Bush NA, et al. Global post-marketing safety surveillance of tumor treating fields (TTFields) in patients with high-grade glioma in clinical practice[J]. J Neurooncol, 2020, 148(3): 489-500. DOI: 10.1007/s11060-020-03540-6.
[42]	Anadkat MJ, Lacouture MR, Friedman A, et al. Expert guidance on prophylaxis and treatment of dermatologic adverse events with tumor treating fields (TTFields) therapy in the thoracic region[J]. Front Oncol, 2023, 12: 975473. DOI: 10.3389/fonc.2022.975473.
[43]	Shah PP, White T, Khalafallah AM, et al. A systematic review of tumor treating fields therapy for high-grade gliomas[J]. J Neurooncol, 2020, 148(3): 433-443. DOI: 10.1007/s11060-020-03563-z.