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Updated: Oct 16, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Tumor-treating fields as a proton beam-sensitizer for glioblastoma therapy
Won Seok Lee1, Seung-Jun Seo2, Hye Kyung Chung3
1Department of Biochemistry, School of Medicine, Daegu Catholic University 33 17-gil, Duryugongwon-ro, Nam-gu, Daegu, Republic of Korea.
Abstract:
Few advances in GBM treatment have been made since the initiation of the Stupp trials in 2005. Experimental studies on immunotherapy drugs, molecular inhibitors, radiation dosage escalation and vascular growth factor blockers have all failed to provide satisfactory outcomes. TTFields therapy, on the other hand, have emerged as a viable substitute to therapies like radiation in GBM patients having a highly immunosuppressive tumor microenvironment. To enhance the biofunctional impacts, we explored the combination events with TTFields and proton treatment in this study. We conducted a cell viability test, a cell death detection evaluation, a ROS analysis, a three-dimensional (3D) culture system, and a migration assay. The combination of proton radiation and TTFields therapy laid a substantial anticancer impact on the F98 and U373 as compared to the consequences of either of these therapies used separately. The combination proton beam therapy used by TTFields was very successful in curbing GBM from migrating. GBM cell metastasis is restricted by TTFields combined proton by downregulating the MAPK, NF-κB, and PI3K/AKT indicating pathways, caused by reduced EMT marker expression. These findings furnish biological proof for the molecular grounds of TTFields in combination with proton used for GBM therapy.
Insights
Combining Tumor Treating Fields (TTFields) therapy with proton radiation significantly enhances anti-cancer effects against glioblastoma (GBM). This novel approach effectively inhibits GBM cell migration and metastasis by modulating key molecular pathways.
Area of Science:
- Oncology
- Biophysics
- Radiation Oncology
Background:
- Glioblastoma (GBM) treatment has seen limited progress since 2005, with many experimental therapies failing to yield satisfactory outcomes.
- Tumor Treating Fields (TTFields) therapy presents a promising alternative for GBM patients, particularly those with immunosuppressive tumor microenvironments.
Purpose of the Study:
- To investigate the synergistic anti-cancer effects of combining TTFields therapy with proton radiation in GBM.
- To elucidate the molecular mechanisms underlying the combined therapy's efficacy in inhibiting GBM cell growth and migration.
Main Methods:
- Cell viability assays, cell death detection, reactive oxygen species (ROS) analysis.
- Three-dimensional (3D) cell culture models and cell migration assays were employed.
- Analysis of key molecular pathways including MAPK, NF-κB, and PI3K/AKT, and epithelial-mesenchymal transition (EMT) markers.
Main Results:
- The combination of proton radiation and TTFields demonstrated a significant anti-cancer impact on F98 and U373 GBM cells, surpassing the effects of either therapy alone.
- Combined therapy effectively inhibited GBM cell migration and metastasis.
- Downregulation of MAPK, NF-κB, and PI3K/AKT pathways, along with reduced EMT marker expression, was observed.
Conclusions:
- The combination of TTFields and proton radiation offers a potent therapeutic strategy for GBM.
- These findings provide a biological and molecular basis for the combined use of TTFields and proton therapy in GBM treatment.
- This approach shows potential for restricting GBM cell metastasis through pathway modulation.
