Tumor Treating Fields (TTFields) increase the effectiveness of temozolomide and lomustine in glioblastoma cell lines

Fishman, Hila; Monin, Roni; Dor-On, Eyal; Kinzel, Adrian; Haber, Adi; Giladi, Moshe; Weinberg, Uri; Palti, Yoram

doi:10.1007/s11060-023-04308-4

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…Patients with MGMT-methylated tumors had superior prognoses, potentially attributable to increased temozolomide (TMZ) sensitivity in these tumors ( 34 ). Notably, recent research on human GBM cell lines indicated a synergistic effect of combining TTFields with chemotherapy agents such as TMZ on MGMT promoter methylated cells ( 35 ). Moreover, our study found no significant prognostic impact from other tumor biomarkers, such as IDH and TERT promoter mutations.…”

Section: Discussionmentioning

confidence: 99%

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors

Wang,

Du,

Chen

et al. 2024

Front. Oncol.

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IntroductionTumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy.MethodsWe have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS.ResultsThe median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0–32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710).ConclusionThe TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

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Section: Discussionmentioning

confidence: 99%

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors

Wang,

Du,

Chen

et al. 2024

Front. Oncol.

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“…TTFields therapy has been authorized for the treatment of newly diagnosed GBM in conjunction with maintenance temozolomide. Recent evidence has shown the efficacy of TMZ when combined with lomustine (CCNU) in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, findings which reinforce the clinical advantage of using TTFields in combination with both temozolomide and lomustine [ 308 ].…”

Section: The Tumor Microenvironment In Gliomas: a Focal Pointmentioning

confidence: 97%

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Onciul,

Brehar,

Toader

et al. 2024

CIMB

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Gliomas constitute a diverse and complex array of tumors within the central nervous system (CNS), characterized by a wide range of prognostic outcomes and responses to therapeutic interventions. This literature review endeavors to conduct a thorough investigation of gliomas, with a particular emphasis on glioblastoma (GBM), beginning with their classification and epidemiological characteristics, evaluating their relative importance within the CNS tumor spectrum. We examine the immunological context of gliomas, unveiling the intricate immune environment and its ramifications for disease progression and therapeutic strategies. Moreover, we accentuate critical developments in understanding tumor behavior, focusing on recent research breakthroughs in treatment responses and the elucidation of cellular signaling pathways. Analyzing the most novel transcriptomic studies, we investigate the variations in gene expression patterns in glioma cells, assessing the prognostic and therapeutic implications of these genetic alterations. Furthermore, the role of epigenetic modifications in the pathogenesis of gliomas is underscored, suggesting that such changes are fundamental to tumor evolution and possible therapeutic advancements. In the end, this comparative oncological analysis situates GBM within the wider context of neoplasms, delineating both distinct and shared characteristics with other types of tumors.

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“…BRCA1 and BRCA2 play an important role in maintaining the fidelity of DNA replication by mediating homologous recombination repair, and downregulation of BRCA gene expression can inhibit DNA double-strand repair. 20 PARP is a protein involved in DNA repair. PARP inhibitor treatment induces cancer cell death in patients with BRCA mutations or defects.…”

Section: Ttfields Inhibit Dna Damage Repairmentioning

confidence: 99%

“…23 The combination of TTFields with sorafenib, TMZ + lomustine, RT, or hyperthermia enhances the apoptosis induced by TTFields. 15,20,24,25…”

Section: Ttfields Induce Apoptosis Of Cancer Cellsmentioning

confidence: 99%

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Theory and application of TTFields in newly diagnosed glioblastoma

Yu,

Zeng,

et al. 2024

CNS Neurosci Ther

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BackgroundGlioblastoma is the most common primary malignant brain tumor in adults. TTFields is a therapy that use intermediate‐frequency and low‐intensity alternating electric fields to treat tumors. For patients with ndGBM, the addition of TTFields after the concurrent chemoradiotherapy phase of the Stupp regimen can improve prognosis. However, TTFields still has the potential to further prolong the survival of ndGBM patients.AimBy summarizing the mechanism and application status of TTFields in the treatment of ndGBM, the application prospect of TTFields in ndbm treatment is prospected.MethodsWe review the recent literature and included 76 articles to summarize the mechanism of TTfields in the treatment of ndGBM. The current clinical application status and potential health benefits of TTFields in the treatment of ndGBM are also discussed.ResultsTTFields can interfere with tumor cell mitosis, lead to tumor cell apoptosis and increased autophagy, hinder DNA damage repair, induce ICD, activate tumor immune microenvironment, reduce cancer cell metastasis and invasion, and increase BBB permeability. TTFields combines with chemoradiotherapy has made progress, its optimal application time is being explored and the problems that need to be considered when retaining the electrode patches for radiotherapy are further discussed. TTFields shows potential in combination with immunotherapy, antimitotic agents, and PARP inhibitors, as well as in patients with subtentorial gliomas.ConclusionThis review summarizes mechanisms of TTFields in the treatment of ndGBM, and describes the current clinical application of TTFields in ndGBM. Through the understanding of its principle and application status, we believe that TTFields still has the potential to further prolong the survival of ndGBM patients. Thus,research is still needed to explore new ways to combine TTFields with other therapies and optimize the use of TTFields to realize its full potential in ndGBM patients.

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Tumor Treating Fields (TTFields) increase the effectiveness of temozolomide and lomustine in glioblastoma cell lines

Cited by 13 publications

References 35 publications

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Theory and application of TTFields in newly diagnosed glioblastoma

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