The Routine Application of Tumor-Treating Fields in the Treatment of Glioblastoma WHO° IV

Krigers, Aleksandrs; Pinggera, Daniel; Demetz, Matthias; Kornberger, Lisa-Marie; Kerschbaumer, Johannes; Thomé, Claudius; Freyschlag, Christian F.

doi:10.3389/fneur.2022.900377

Cited by 9 publications

(6 citation statements)

References 60 publications

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“…Over the past decade, TTFields have emerged as a complementary treatment strategy, which is now part of the SOC in GB treatment [ 289 , 326 , 327 , 328 ]. The FDA’s approval of rGB was based on the results from the EF-11 trial (NCT00379470) showing that TTFields monotherapy provided similar efficacy compared to the best physician’s choice chemotherapy in patients with rGB, albeit with better quality of life, less toxicity and a lower incidence of serious adverse events [ 329 ].…”

Section: Present Therapy and Challengesmentioning

confidence: 99%

“…The addition of TTFields to the SOC therapy improved median OS (mOS) from 15.6 to 20.5 months without a negative influence on the health-related quality of life [ 13 , 330 , 331 ]. In ndGB, TTFields are applied within 6 weeks after the end of the radio-chemotherapy, ideally simultaneously with TMZ monotherapy [ 13 , 328 ]. Patients with compliance > 90% showed extended median and 5-year survival rates [ 256 ].…”

Section: Present Therapy and Challengesmentioning

confidence: 99%

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Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Present Therapy and Challengesmentioning

confidence: 99%

Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…[ 28 ] Indeed, in Krigers et al . [ 20 ], trial patients treated with TTFields within six weeks after concomitant chemoradiotherapy (Stupp protocol) showed an OS significantly favorable in the case of MGMT promoter methylation. On the contrary, IDH status did not change OS (LogRank P = 0.549 IDH-mutation and IDH wild-type).…”

Section: Role Of Ttfields In Ngbmmentioning

confidence: 99%

“…Nonetheless, a stronger TTFields effect was shown following RT, possibly since TTFields delay the repair of DNA damage induced by conventional photon beam radiotherapy, making cells more vulnerable. [ 20 , 29 ]…”

Section: Role Of Ttfields In Ngbmmentioning

confidence: 99%

Tumor treating fields for the treatment of glioblastoma: Current understanding and future perspectives

Colamaria,

Leone,

Fochi

et al. 2023

Surgical Neurology International

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Background: This review focuses on the recently published evidence on tumor treating fields (TTFields) administered alone or in combination with locoregional and systemic options for treating glioblastoma (GBM) in the past ten years. The aim is to critically summarize the novelty and results obtained with this innovative tool, which is becoming part of the armamentarium of neurosurgeons and neuro-oncologists. Methods: A comprehensive search and analysis were conducted on pivotal studies published in the past ten years. Furthermore, all completed clinical trials, whose results were published on clinicaltrials.gov, were examined and included in the present review, encompassing both recurrent (r) and newly diagnosed (n) GBM. Finally, an additional examination of the ongoing clinical trials was also conducted. Results: Recent trials have shown promising results both in patients with nGBM and rGBM/progressive (rGBM), leading to Food and Drug Administration approval in selected patients and the Congress of Neurological Surgeons to include TTFields into current guidelines on the management of GBM (P100034/S001-029). Recently, different randomized trials have demonstrated promising results of TTFields in combination with standard treatment of n- and rGBM, especially when considering progression-free and overall survival, maintaining a low rate of mild to moderate adverse events. Conclusion: Optimal outcomes were obtained in nGBM and progressive disease. A possible future refinement of TTFields could significantly impact the treatment of rGBM and the actual standard of care for GBM, given the better safety profile and survival effects.

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“…185,186 At least some treatment centres have incorporated TTFields into their standard of care despite their high costs. 185,187 As well as the expense, the visibility of the device, which must be worn on the shaved scalp for 18 hours a day, is a major factor in the fairly low patient acceptance of the treatment (36% in a 2018 study). 188 However, compliance rates in patients who choose TTFields treatment are high and skin irritation due to the device is the only adverse effect in addition to those already induced by TMZ.…”

Section: 16: Other Gbm Treatmentsmentioning

confidence: 99%

BCL6 is a context-dependent mediator of the glioblastoma therapy response

Tribe¹

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<p>Glioblastoma is a rapidly fatal brain cancer with no cure. The resistance of glioblastoma tumours to available therapies means that more effective treatments are desperately needed. Previous research showed that the transcriptional repressor protein BCL6 is upregulated by chemo- and radiotherapy in glioblastoma and that inhibition of BCL6 enhances the effectiveness of these therapies. Therefore, BCL6 is a promising target to improve the efficacy of available treatments for glioblastoma. BCL6 is known as a transcriptional repressor in germinal centre B cells and an oncogene in lymphoma, as well as in other cancers. However, previous research indicated that BCL6 induced by therapy in glioblastoma may not act as a transcriptional repressor. This thesis aimed to clarify the role of BCL6 in the therapy response of glioblastoma. The effect of BCL6 inhibition on the whole proteome response of glioblastoma cells to DNA-damaging treatments was investigated. This confirmed that BCL6 was involved in the therapy response of glioblastoma and that acute irradiation appeared to cause BCL6 to switch from a repressor of the DNA damage response to a promoter of stress response signalling. Rapid immunoprecipitation mass spectrometry of endogenous proteins enabled identification of proteins associated with BCL6 in untreated and irradiated glioblastoma cells. BCL6 appeared to be a transcriptional regulator in untreated glioblastoma and its association with the corepressor NCOR2 was validated using proximity ligation assays. However, association with nuclear proteins was lost in response to acute irradiation. This was accompanied by the irradiation-induced association of BCL6 with plasma membrane proteins. Targeted long-read transcript sequencing did not reveal differential alternative splicing of BCL6 in response to acute irradiation. This indicated that the canonical BCL6 protein was expressed in irradiated glioblastoma cells and that the change in BCL6 function must be mediated by mechanisms other than the production of splice variants, such as through post-translational modification. Overall, these results support the hypothesis that BCL6 is involved in the therapy resistance of glioblastoma cells but reveal that its activity is context-dependent and may be mediated by the intensity of cellular stress.</p>

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The Routine Application of Tumor-Treating Fields in the Treatment of Glioblastoma WHO° IV

Cited by 9 publications

References 60 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

Tumor treating fields for the treatment of glioblastoma: Current understanding and future perspectives

BCL6 is a context-dependent mediator of the glioblastoma therapy response

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