肿瘤治疗电场在胶质母细胞瘤治疗中的应用进展

doi:10.11904/j.issn.1002-3070.2025.04.015

摘要/Abstract

摘要： 胶质母细胞瘤(glioblastoma,GBM)是最常见的颅内恶性肿瘤,具有恶性程度高、复发率高和预后差等特点。目前,复发性GBM仍缺乏统一的治疗方案。GBM患者在接受了包括最大安全范围切除术、术后同步放化疗及替莫唑胺辅助化疗在内的标准治疗后,其中位生存期仅为14.6个月。近年研究表明,肿瘤治疗电场(tumor treating field,TTField)作为新型物理治疗手段,可显著延长患者生存期并改善生活质量。本文系统阐述TTField在GBM中的抗肿瘤作用机制,重点分析其与放化疗、靶向治疗及免疫治疗的协同效应,并探讨临床应用面临的挑战与发展前景。

关键词: 肿瘤治疗电场, 胶质母细胞瘤, 联合治疗

Abstract: Glioblastoma(GBM)is the most common intracranial malignant tumor,characterized by high malignancy,high recurrence rate,and poor prognosis.Currently,there is still a lack of unified treatment plan for recurrent GBM.After receiving standard treatment including maximum safe resection,postoperative concurrent radio-chemotherapy,and temozolomide adjuvant chemotherapy,the median survival time of GBM patients was only 14.6 months.Recent studies have shown that tumor treating fields(TTFields),as a novel physical therapeutic approach,can significantly prolong patient survival and improve quality of life.This article systematically elaborates on the antitumor mechanism of TTFields in GBM,with a focus on analyzing its synergistic effects with radiotherapy,chemotherapy,targeted therapy,and immunotherapy,and exploring the challenges and development prospects of clinical application.

Key words: Tumor treated with electric field, Glioblastoma, Combination therapy

中图分类号:

R739.4

曹晶晶, 张弓. 肿瘤治疗电场在胶质母细胞瘤治疗中的应用进展[J]. 实用肿瘤学杂志, 2025, 39(4): 353-357.

CAO Jingjing, ZHANG Gong. Progress in the application of electric field therapy for tumor in the treatment of glioblastoma[J]. Journal of Practical Oncology, 2025, 39(4): 353-357.

参考文献

1 Alphandéry E.Glioblastoma treatments:an account of recent industrial developments[J].Front Pharmacol,2018,9:879.
2 Wen PY,Weller M,Lee EQ,et al.Glioblastoma in adults:a Society for Neuro-Oncology(SNO)and European Society of Neuro-Oncology(EANO)consensus review on current management and future directions[J].Neuro-Oncology,2020,22(8):1073-1113.
3 Armstrong DK,Alvarez RD,Bakkum-Gamez JN,et al.Ovarian cancer,version 2.2020,NCCN clinical practice guidelines in oncology[J].J Natl ComprCanc Netw,2021,19(2):191-226.
4 国家卫生健康委员会医政医管局.脑胶质瘤诊疗规范(2018年版)[J].中华神经外科杂志,2019,35(3):217-239.
5 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-UK,2015,5:18046.
6 Moser JC,Salvador E,Deniz K,et al.The mechanisms of action of tumor treating fields[J].Cancer Res,2022,82(20):3650-3658.
7 Roominess O,Vanderbilt A,Clinton SJ,et al.Tumour treating fields therapy for retinoblastoma:current advances and future directions[J].Br.J.Cancer,2021,124(4):697-709.
8 Kirson ED,Gurvich Z,Schneiderman R,et al.Disruption of cancer cell replication by alternating electric fields[J].Cancer Res,2004,64(9):3288-3295.
9 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.
10 Suknuntha K,Ishii Y,Tao L,et al.Discovery of survival factor for primitive chronic myeloid leukemia cells using induced pluripotent stem cells[J].Stem Cell Res,2015,15(3):678-693.
11 Giladi M,Schneiderman RS,Porat Y,et al.Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields[J].Pancreatology,2014,14(1):54-63.
12 Shteingauz A,Porat Y,Voloshin T,etal.AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields(TTFields)[J].Cell Death Dis,2018,9(11):1074.
13 Kirson ED,Dbaly V,Tovarys F,et al.Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors[J].PNAS Academy of Sciences of the United Statesof America,2007,104(24):10152-10157.
14 Silginer M,Weller M,Stupp R,Roth P.Biological activity of tumor-treating fields in preclinical glioma models[J].Cell Death Dis,2017,8(4):e2753.
15 Stupp R,Wong ET,Kanner AA,et al.NovoTTF-100A versus physician′s choice chemotherapy in recurrent glioblastoma:a randomised phase III trial of a novel treatment modality[J].Eur J Cancer,2012,48(14):2192-2202.
16 Kondo N,Takahashi A,Ono K,et al.DNA damage induced by alkylating agents and repair pathways[J].J Nucleic Acids,2010,2010:543531.
17 Michelhaugh S,Degen K,Walker B,et al.In vitro tumor treating fields(TTFields)reduce proliferation and alter MLH1 expression in temozolomide-resistant(TMZR)patient-derived glioblastome(GBM)cells[J].Neuro-Oncology,2021,23(Supplement-6):vi27.
18 Fishman H,Monin R,Dor-On E,et al.Tumor Treating Fields(TTFields)increase the effectiveness of temozolomide and lomustine in glioblastoma cell lines[J].J Neurooncol,2023,163(1):83-94.
19 Nahm J,Sinha M,Schumann EH,et al.Overall survival in patients with recurrent glioblastomas with combination chemotherapy and tumor treating fields(TTF)[J].J Clin Oncol,2023,41(16):e14057.
20 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.
21 Luo XS,Zhong YL,Xu SY,et al.Meta-analysis of the clinical efficacy of tumor treating fields combined with temozolomide chemotherapy and temozolomide chemotherapy alone for glioblastoma[J].J Int Neurol Neurosurg,2020,47(6):595-601.
22 Kirson ED,Schneiderman RS,Dbaly V,et al.Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields(TTFields)[J].BMC Med Phys,2009,9:1.
23 Stupp R,Taillibert S,Kanner AA,et al.Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma:a randomized clinical trial[J].Jama,2015,314(23):2535-2543.
24 Chang E,Pohling C,Beygui N,et al.Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields[J].J Neurooncol,2017,134:259-268.
25 Kebir S,Lazaridis L,Schmidt T,et al.Safety and efficacy of tumor treating fields(TTFields)prior and concomitant to radiotherapy in patients with newly diagnosed glioblastoma:Results from PriCoTTF[J].J Clin Oncol,2023,41(16_suppl):2050.
26 Karanam NK,Srinivasan K,Ding L,et al.Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines[J].Cell Death Dis,2017,8(3):e2711.
27 Bokstein F,Blumenthal D,Limon D,et al.Concurrent tumor treating fields(TTFields)and radiation therapy for newly diagnosed glioblastoma:a prospective safety and feasibility study[J].Front Oncol 2020,10:411.
28 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,2017,12:1-13.
29 Tu J,Fang Y,Han D,et al.Activation of nuclear factor-κB in the angiogenesis of glioma:Insights into the associated molecular mechanisms and targeted therapies[J].Cell Prolif,2021,54(2):e12929.
30 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.
31 Fallah J,Chaudhary RT,Rogers LR,et al.Clinical outcomes of the combination of bevacizumab and ttfields in patients with recurrent glioblastoma:Results of a phase II clinical trial[J].J Neurooncol,2020,149(2):2537-2544.
32 Elzinga G,Chung AT,Wong E.Safety analysis of bevacizumab plus NovoTTF-100A in patients with recurrent malignant gliomas[J].Neuro Oncol,2015,17:v174.
33 Qian K,Li G,ZhangG S,et al.CAR-T-cell products in solid tumors:Progress,challenges,and strategies[J].Interdiscip Med,2024,2(2):e20230047.
34 Lu G,Rao M,Zhu P,et al.Triple-drug therapy with bevacizumab,irinotecan,and temozolomide plus tumor treating fields for recurrent glioblastomaa retrospective study[J].Front Neurol,2019,10:42.
35 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 Immun,2020,69(7):1191-1204.
36 Diamant G,Simchony Goldman H,Gasri Plotnitsky L,et al.T Cells retainpivotal antitumoral functions under tumor-treating electric fields[J].J Immunol,2021,207(2):709-719.
37 Shoddy J,Instrument A,Velazquez A,et al.CTIM-17.Phase I study of the safety and carcinogenicity of personalized antigen vaccines and tumor treating fields in patients with newly diagnosed retinoblastoma[J].Euro-Oncology,2020,22(Suppl 2):ii36.
38 Ali AS,Lombardo J,Niazi MZ,et al.Concurrent chemoradiation and tumor treating fields(ttfields,200 kHz)for patients with newly diagnosed glioblastoma:patterns of progression in a single institution pilot study[J].J Neuro-Oncol,2022,160(2):345-350.
39 Li Z,Bhang X,Que T,et al.Fields combined with thalidomide and Hypnotherapy show long-term PFS on a GBM patients with multiple negative prognostic factors[J].Cancer Res,2023,83(7_Supplement):3252.
40 Korshoej AR,Lukacova S,Lassen-Ramshad Y,et al.OptimalTTF-1:Enhancing tumor treating fields therapy withskull remodeling surgery.A clinical phase I trial in adult recurrent glioblastoma[J].Neurooncol Adv,2020,2(1):vdaa121.
41 Connock M,Auguste P,Dussart C,et al.(2019).Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma:an updated evaluation using a partitioned survival model[J].J Neuro oncol,143:605-611.
42 Lacouture ME,Anadkat MJ,Ballo MT,et al.Prevention and management of dermatologic adverse events associated with tumor treating fields in patients with glioblastoma[J].Front Oncol,2020,10:1045.
43 Anadkat MJ,Lacouture M,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.
44 Mrugala MM,Shi W,Iwamoto F,et al.Global post marketing safety surveillance of Tumor Treating Fields(TTFields)therapy in over 25,000 patients with CNS malignancies treated between 2011-2022[J].J Neurooncol,2024,169(1):25-38.

[1]	赵恩桐, 关心, 李洪艳, 邱韵婷, 张炳强, 陈梦梦, 邹伟, 屈超. SNG162通过上调ER-α36表达激活胶质母细胞瘤膜起始的雌激素信号通路[J]. 实用肿瘤学杂志, 2025, 39(3): 177-183.
[2]	唐冬, 高文宏, 张华平, 陈谦学. 桑辛素对胶质瘤细胞株U87迁移与侵袭的影响[J]. 实用肿瘤学杂志, 2024, 38(3): 168-172.
[3]	王丙萍, 段金凯, 张双, 高艳伟, 任猛, 陈良全, 高维实. NK细胞联合PD-1单抗杀伤结直肠癌细胞的研究[J]. 实用肿瘤学杂志, 2023, 37(2): 130-136.
[4]	童曼琳, 尚茹茹, 刘晓红. PD-1/PD-L1免疫检查点抑制剂在多形性胶质母细胞瘤中的研究进展[J]. 实用肿瘤学杂志, 2022, 36(3): 278-282.
[5]	刘金爽, 张文静, 黎清炜, 李志伟. 免疫检查点抑制剂的联合治疗在胰腺癌中的研究进展[J]. 实用肿瘤学杂志, 2022, 36(1): 49-53.
[6]	石琳娜, 隋红. 原发性肝癌免疫检查点抑制剂治疗的进展与挑战[J]. 实用肿瘤学杂志, 2020, 34(6): 560-564.
[7]	白晓斌, 霍龙伟, 谢万福, 徐高峰, 王茂德. Chk1在胶质母细胞瘤中的表达及其与肿瘤生物学行为和预后生存的关联性[J]. 实用肿瘤学杂志, 2019, 33(2): 122-127.
[8]	徐延斌,麻旭东,谢晨,詹奇,任付宾. 脑胶质瘤中RAD18的表达与放射治疗抵抗相关性分析[J]. 实用肿瘤学杂志, 2017, 31(4): 289-293.
[9]	刘恩瑞,任欢,赵宇(综述),苏君(审校). 胶质母细胞瘤经典亚型特征性基因变异的研究进展[J]. 实用肿瘤学杂志, 2015, 29(2): 136-139.
[10]	徐延斌(综述),李建华(审校). 放射性粒子治疗与基因治疗神经胶质瘤的概况[J]. 实用肿瘤学杂志, 2015, 29(2): 153-156.
[11]	王法综述,王宏辉审校. 肝动脉化疗栓塞术联合射频消融术治疗小肝癌的研究进展[J]. 实用肿瘤学杂志, 2013, 27(5): 447-451.
[12]	常亮综述, 苏君审校. 原发与继发性胶质母细胞瘤相关基因表达分析^△[J]. 实用肿瘤学杂志, 2008, 22(6): 557-561.