Han Wei, Chen Liang
Neurosurgical Department of Huashan Hospital and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
Tianqiao and Chrissy, Chen Institute Clinical Translational Research Center, Shanghai, 200032, China.
Clin Transl Oncol. 2025 Apr 14. doi: 10.1007/s12094-025-03909-x.
Malignancies in the central nervous system (CNS) are among the most prevalent and lethal tumors. Tumor treating fields (TTFields), a physical therapeutic strategy, show significant potential in treating CNS tumors by inducing cell apoptosis, cell-cycle arrest, immune activation, and enhancing anti-PD-1 therapy efficacy. Additionally, TTFields can increase blood-brain barrier (BBB) permeability, further supporting their application in CNS malignancies. This review aims to summarize the advances and mechanisms of TTFields in CNS tumor treatment while addressing its current limitations and challenges.
We reviewed existing literature on TTFields, focusing on their effects on glioma and brain metastasis (BM)-related primary tumors. The mechanisms investigated included mitosis and cell cycle interference, inhibition of cell migration and invasion, promotion of apoptosis and protective autophagy, activation of immunogenic cell death (ICD) and immune responses, and modulation of BBB permeability.
TTFields demonstrate inhibitory effects on CNS malignancies, particularly in glioma. They also suppress brain metastasis from primary tumors such as lung cancer, breast cancer, melanoma, and colorectal cancer. Mechanistically, TTFields act through multiple pathways, including disrupting mitosis, impeding cell migration and invasion, enhancing apoptosis and autophagy, activating immune responses, and increasing BBB permeability.
TTFields exhibit therapeutic potential in CNS malignancies, especially glioblastoma (GBM), through diverse biological mechanisms. Their ability to enhance BBB permeability and target metastatic tumors suggests promise for broader clinical applications, including brain metastasis treatment.
中枢神经系统(CNS)恶性肿瘤是最常见且致命的肿瘤之一。肿瘤治疗电场(TTFields)作为一种物理治疗策略,通过诱导细胞凋亡、细胞周期阻滞、免疫激活以及增强抗程序性死亡蛋白1(PD-1)治疗效果,在治疗CNS肿瘤方面显示出巨大潜力。此外,TTFields可增加血脑屏障(BBB)通透性,进一步支持其在CNS恶性肿瘤中的应用。本综述旨在总结TTFields在CNS肿瘤治疗中的进展和机制,同时探讨其当前的局限性和挑战。
我们回顾了关于TTFields的现有文献,重点关注其对胶质瘤和脑转移(BM)相关原发性肿瘤的影响。研究的机制包括有丝分裂和细胞周期干扰、细胞迁移和侵袭的抑制、凋亡和保护性自噬的促进、免疫原性细胞死亡(ICD)和免疫反应的激活以及BBB通透性的调节。
TTFields对CNS恶性肿瘤具有抑制作用,尤其是在胶质瘤中。它们还可抑制肺癌、乳腺癌、黑色素瘤和结直肠癌等原发性肿瘤的脑转移。从机制上讲,TTFields通过多种途径发挥作用,包括破坏有丝分裂、阻碍细胞迁移和侵袭、增强凋亡和自噬、激活免疫反应以及增加BBB通透性。
TTFields通过多种生物学机制在CNS恶性肿瘤,尤其是胶质母细胞瘤(GBM)中展现出治疗潜力。其增强BBB通透性和靶向转移性肿瘤的能力表明在包括脑转移治疗在内的更广泛临床应用中具有前景。