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Tumor Discovery Glioblastoma treating fields system

aggressive treatment approaches, including surgery, these mechanisms is crucial for refining TTF parameters to
radiation, and chemotherapy, the prognosis for GBM enhance its therapeutic effectiveness and integrate it with
patients remains dismal, with a median survival time of other emerging treatments, such as immunotherapy and
only 12 – 15 months. The challenges in treating GBM targeted drug delivery systems.
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lie in its highly invasive nature, rapid proliferation, and To address these limitations, our study presents the
resistance to standard therapies. Current therapies are design, development, and preclinical evaluation of a novel
often limited by the blood-brain barrier, which restricts TTF system, focusing on key components such as electrical
the delivery of chemotherapeutic agents, as well as the signal regulation, transmission, and corresponding
tumor’s heterogeneity, which leads to treatment failure and therapeutic effects. We designed the system to generate
recurrence. 5 highly controlled electric fields and incorporated it with
The standard treatment regimen for GBM, known as the high-dielectric ceramic electrodes composed of barium
Stupp protocol, includes maximal safe surgical resection titanate zirconate, 27-29 which have superior electric field
followed by radiotherapy and concurrent temozolomide transmission properties compared to conventional
chemotherapy. Although this approach slightly extends electrodes. By evaluating the performance of this system
6,7
survival, the 5-year survival rate of patients typically through in vitro glioblastoma cell experiments and in vivo
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remains below 10%, underscoring the urgent need for novel rat models, we demonstrate its efficacy in inhibiting tumor
therapeutic strategies. Moreover, extensive infiltration of growth. Furthermore, we provide a comprehensive guide
GBM into healthy brain tissue renders complete surgical to the technical design of the system to further democratize
removal nearly impossible, necessitating adjuvant therapies TTF research more accessible with the hope to deepen
capable of targeting residual tumor cells without causing innovation in the field.
significant toxicity to the surrounding brain structures. 9 This study contributes valuable insights into the
Tumor treating fields (TTF) have emerged as a optimization of TTF therapy for clinical use, particularly
promising non-invasive therapeutic modality for GBM, in enhancing the effectiveness of electric field-based
offering an alternative mechanism to target tumor cancer treatments. In addition, we explore how electric
growth. 10-12 TTF utilizes low-intensity, alternating electric field intensity, frequency, and electrode design impact
fields at intermediate frequencies (100 – 300 kHz) to treatment outcomes, providing data that could inform
disrupt the mitotic process of rapidly dividing tumor cells. future advancements in personalized TTF therapy.
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These fields interfere with microtubule polymerization, Our approach integrates interdisciplinary expertise in
alignment of chromosomes, and other essential mitotic engineering, materials science, and oncology, positioning
functions, leading to apoptosis. 14,15 The U.S. Food and this study as a crucial step toward improving the clinical
Drug Administration (FDA) has approved the use of TTF application of TTF therapy. By systematically analyzing
therapy through devices like the Optune system, further treatment parameters and their biological effects, we
validating its potential in GBM treatment. Clinical trials aim to bridge the gap between experimental and clinical
have demonstrated the ability of TTF therapy to prolong applications, ultimately refining TTF therapy as a viable
overall survival and progression-free survival in GBM component of multimodal GBM treatment strategies.
patients when combined with standard chemoradiation. 16-18 Beyond the immediate implications for GBM
However, the full potential of TTF has yet to be realized, as treatment, the principles underlying TTF therapy may
current systems are limited in their flexibility to adjust field hold broader applications in other malignancies, including
parameters, and few studies have explored the detailed lung, 30,31 pancreatic, 32,33 and ovarian 34,35 cancers. Future
engineering behind the design and optimization of TTF research should explore the feasibility of expanding TTF
systems. technology to different cancer types, optimizing electrode
configurations, and integrating real-time monitoring
Despite its promising efficacy, TTF therapy is systems to enhance treatment precision. By advancing TTF
constrained by several limitations, including patient system design and understanding its mechanistic effects,
adherence to continuous treatment (at least 18 h/day), we hope to contribute to the development of more effective,
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variability in treatment response due to anatomical and personalized, and patient-friendly cancer therapies.
tumor heterogeneity, and potential skin irritation from
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electrode placement. In addition, the precise biophysical 2. Materials and methods
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mechanisms underlying TTF therapy remain an active area
of research, with emerging studies investigating its broader 2.1. Materials and instruments
impact on cell signaling pathways, immune modulation, The reagents used in the cell experiments comprised
and the tumor microenvironment. 21-26 Understanding glioblastoma cells (Cyagen Biosciences), Dulbecco’s

Volume 4 Issue 2 (2025) 56 doi: 10.36922/td.7171