Multiomics Insights into the Mechanism and Enhanced Efficacy of Tumor Treating Fields (TTFields) Therapy in Glioblastoma
文献类型：期刊论文
| 作者 | Gao, Yanmei4,5; Wang, Chenxu4,5; Liu, Guobin5; Zhang, Ruilin3; Ren, Xuelian3,5; Hu, Guangyuan1; Mei, Qi1; Huang, He2,3,4,5 |
| 刊名 | JOURNAL OF PROTEOME RESEARCH
 |
| 出版日期 | 2025-09-01 |
| 页码 | 15 |
| 关键词 | tumor treating fields glioblastoma proteomics phosphoproteomics glycoproteomics |
| ISSN号 | 1535-3893 |
| DOI | 10.1021/acs.jproteome.5c00424 |
| 通讯作者 | Hu, Guangyuan(h.g.y.121@163.com) ; Mei, Qi(borismq@163.com) ; Huang, He(hhuang@simm.ac.cn) |
| 英文摘要 | Glioma is an aggressive brain tumor that requires challenging treatments. Tumor Treating Fields (TTFields), an FDA-approved therapy for glioblastoma (GBM), pleural mesothelioma, and platinum-refractory metastatic nonsmall cell lung cancer (in combination with PD-1/PD-L1 inhibitors or docetaxel), employs specific frequency electric fields to disrupt cell division and enhance treatment efficacy. However, their molecular mechanisms remain unclear. This study aimed to elucidate these mechanisms and optimize the therapeutic potential of TTFields through quantitative proteomics, phosphoproteomics, and glycoproteomics. Pathway analysis of the proteomics revealed that TTFields impact the cell cycle, DNA repair, autophagy, and DNA replication. Phosphoproteomic studies further demonstrated a marked decline in the activity of key kinases ABL1 and PDK1, while glycoproteomics highlighted disruptions in cell adhesion and ECM-receptor interactions. Notably, proteomic analysis identified an upregulation of PARP1 and BRD4 protein levels, suggesting a previously unrecognized resistance mechanism. Consistently, combining TTFields with inhibitors targeting these proteins significantly enhanced the treatment efficacy in U87 cells. Thus, this study uncovers comprehensive molecular mechanisms underlying TTFields' effects on GBM cells and supports the development of concomitant therapies to enhance treatment efficacy. |
| WOS关键词 | PROTEIN-KINASE CK2 ; CENTRAL-NERVOUS-SYSTEM ; DNA-DAMAGE ; CANCER ; REPLICATION ; BRAIN |
| 资助项目 | Natural Science Foundation of Shanghai Municipality[XDB1060000] ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Shanghai Municipal Science and Technology Major Project[22277125] ; Shanghai Municipal Science and Technology Major Project[92253306] ; National Natural Science Foundation of China[23ZR1474600] ; Natural Science Foundation of Shanghai[ZR2024MB112] ; Shandong Provincial Natural Science Foundation[SYS202205] ; Shandong Laboratory Program ; Research Funds of Hangzhou Institute for Advanced Study UCAS |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001563034900001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321360]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Guangyuan; Mei, Qi; Huang, He |
| 作者单位 | 1.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Oncol, Wuhan 430030, Peoples R China 2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Materia Med, Nanjing 210023, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Yanmei,Wang, Chenxu,Liu, Guobin,et al. Multiomics Insights into the Mechanism and Enhanced Efficacy of Tumor Treating Fields (TTFields) Therapy in Glioblastoma[J]. JOURNAL OF PROTEOME RESEARCH,2025:15. |
| APA | Gao, Yanmei.,Wang, Chenxu.,Liu, Guobin.,Zhang, Ruilin.,Ren, Xuelian.,...&Huang, He.(2025).Multiomics Insights into the Mechanism and Enhanced Efficacy of Tumor Treating Fields (TTFields) Therapy in Glioblastoma.JOURNAL OF PROTEOME RESEARCH,15. |
| MLA | Gao, Yanmei,et al."Multiomics Insights into the Mechanism and Enhanced Efficacy of Tumor Treating Fields (TTFields) Therapy in Glioblastoma".JOURNAL OF PROTEOME RESEARCH (2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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