Glioblastoma — treatment and obstacles

Cantidio, Farley Soares; Gil, Gabriel Oliveira Bernardes; Queiroz, Izabella Nobre; Regalin, Marcos

doi:10.5603/rpor.a2022.0076

Cited by 12 publications

(15 citation statements)

References 64 publications

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“… 25 Although the treatment of GBM has evolved over the years, most patients with GBM still have a very poor prognosis, with a 5-year relative survival rate of 5%. 26 TMZ is a common clinical chemotherapy for GBM, which can cross the blood–brain barrier and trigger tumor cell apoptosis; 27 however, resistance to TMZ develops quickly and frequently. In the current study, we found that ectopic expression of UBE2T decreases TMZ-induced GBM cell apoptosis, whereas UBE2T knockdown induces apoptosis.…”

Section: Discussionmentioning

confidence: 99%

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

Wang¹,

Gao²,

Wei³

et al. 2023

DDDT

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Purpose Patients with glioblastoma (GBM) have poor prognosis and limited therapeutic options, largely because of chemoresistance to temozolomide (TMZ) treatment. Ubiquitin conjugating enzyme E2 T (UBE2T) plays a key role in regulating the malignancy of various tumors, including GBM; however, its role in TMZ resistance of GBM has not been elucidated. The purpose of this study was to clarify the role of UBE2T in mediating TMZ resistance and investigate the specific underlying mechanism. Methods Western blotting was used to detect the protein levels of UBE2T and Wnt/β-catenin-related factors. CCK-8, flow cytometry, and colony formation assays were used to examine the effect of UBE2T on TMZ resistance. Wnt/β-catenin signaling pathway activation was inhibited using XAV-939, and a xenograft mouse model was generated to clarify the function of TMZ in vivo. Results UBE2T knockdown sensitized GBM cells to TMZ treatment, whereas UBE2T overexpression promoted TMZ resistance. The specific UBE2T inhibitor, M435-1279, increased the sensitivity of GBM cells to TMZ. Mechanistically, our results demonstrated that UBE2T induces β-catenin nuclear translocation and increases the protein levels of downstream molecules, including survivin and c-Myc. Inhibition of Wnt/β-catenin signaling using XAV-939 blocked TMZ resistance due to UBE2T overexpression in GBM cells. In addition, UBE2T was shown to facilitate TMZ resistance by inducing Wnt/β-catenin signaling pathway activation in a mouse xenograft model. Combined treatment with TMZ and UBE2T inhibitor achieved superior tumor growth suppression relative to TMZ treatment alone. Conclusion Our data reveal a novel role of UBE2T in mediating TMZ resistance of GBM cells via regulating Wnt/β-catenin signaling. These findings indicate that targeting UBE2T has promising potential to overcome TMZ resistance of GBM.

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Section: Discussionmentioning

confidence: 99%

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

Wang¹,

Gao²,

Wei³

et al. 2023

DDDT

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“…Gene abnormalities are detected in some chromosomes, which might influence cancer progression. [ 2 , 3 ] However, the cause of those abnormalities is undetermined. Many researchers have analyzed the genetic, familial, occupational, and environmental factors for identifying the associations among these factors and gliomas in various cases.…”

Section: Discussionmentioning

confidence: 99%

“…[ 2 ] The treatment of glioblastoma is mainly surgical resection, and radiotherapy and chemotherapy are the most important comprehensive treatments. [ 3 ] The median survival of glioblastoma is over 14 months in patients who are treated following the standardized STUPP regimen (surgery plus temozolomide-based adjuvant chemotherapy, as well as radiotherapy).…”

Section: Introductionmentioning

confidence: 99%

Apatinib combined with temozolomide treatment for pseudoprogression in glioblastoma: A case report

Zhao

Cheng

et al. 2022

Medicine

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Rationale: Glioblastoma is the most common malignant tumor of the central nervous system, which originates from glial cells and corresponding precursors. Due to its strong invasion and rapid growth, the prognosis of patients after treatment is very poor and easy to relapse.Patient concerns: In August 2015, a 48 years old man with a relapse of glioblastoma.Diagnoses: The patient was diagnosed by computed tomography, magnetic resonance imaging, and pathological biopsy in this case report. Interventions:The patient underwent 2 surgeries, radiotherapy, and multiple regular chemotherapy sessions over the next 6 years. Apatinib, an inhibitor of vascular endothelial growth factor receptor 2 was given to treat recurrent glioma.Outcomes: It was found that radiotherapy combined with temozolomide administration often increased the size of the original lesion or produced a new glioblastoma lesion. The lesion development was similar to tumor progression, which was called pseudoprogression. And it significantly prolonged the survival of this patient.Lessons: Surgery, radiotherapy and chemotherapy with apatinib and temozolomide are effective to treat the patients with pseudoprogression in glioblastoma.

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“…In the per-protocol population, the median OS was 8.1 months with TTFields versus 6.5 months with EF-11 BSC (p = 0.045), further supporting the benefit of TTFields. The incidence of adverse events (AE) was lower with TTFields (67%) compared to EF-11 BSC (95%), and the median time to treatment failure was longer in the TTFields arm (3.3 months) versus the BSC arm (1.6 months) (HR = 0.53, 95% CI 0.41-0.68, p < 0.0001) ( 43 ).…”

Section: Ttfields In Gbm Treatmentmentioning

confidence: 99%

Enhancing glioblastoma treatment through the integration of tumor-treating fields

Szklener,

Bilski,

Nieoczym

et al. 2023

Front. Oncol.

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Glioblastoma (GBM) represents a significant therapeutic challenge due to its aggressive nature. Tumor Treating Fields (TTFields) present a promising approach to GBM therapy. The primary mechanism of TTFields, an antimitotic effect, alongside numerous indirect effects including increased cell membrane permeability, signifies their potential in combination with other treatment modalities. Current combinations often include chemotherapy, particularly with temozolomide (TMZ), however, emerging data suggests potential synergy with targeted therapies, radiotherapy, and immunotherapy as well. TTFields display minimal side effects, predominantly skin-related, posing no significant barrier to combined therapies. The effectiveness of TTFields in GBM treatment has been demonstrated through several post-registration studies, advocating for continued research to optimize overall survival (OS) and progression-free survival (PFS) in patients, as opposed to focusing solely on quality of life.

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Glioblastoma — treatment and obstacles

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited.

Cited by 12 publications

References 64 publications

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

Apatinib combined with temozolomide treatment for pseudoprogression in glioblastoma: A case report

Enhancing glioblastoma treatment through the integration of tumor-treating fields

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