Efficacy and Safety of Bevacizumab for Treating Glioblastoma: A Systematic Review and Meta-Analysis of Phase II and III Randomized Controlled Trials

Xie, Xiaohong; Bao, Shangyi; Zhao, Hong; Li, Liuying; Fu, Xiaojun

doi:10.1080/07357907.2023.2174261

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…The OS was not longer than the typical median OS of 12–15 months observed in patients with recurrent GBM receiving the current standard of care . Additionally, the established Stupp protocol and emerging novel treatments, such as biological treatment with Bevacizumab, further expanded the therapeutic options and reduced the reliance on radioimmunotherapy using beta-emitter-labeled antitenascin antibodies. The use of alpha-emitter-labeled 81C6 for TRT in GBM has been limited.…”

Section: Trt Applications For Gbmmentioning

confidence: 91%

Targeted Radionuclide Therapy in Glioblastoma

Zhao,

Jakobsson,

Tao

et al. 2024

ACS Appl. Mater. Interfaces

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Despite the development of various novel therapies, glioblastoma (GBM) remains a devastating disease, with a median survival of less than 15 months. Recently, targeted radionuclide therapy has shown significant progress in treating solid tumors, with the approval of Lutathera for neuroendocrine tumors and Pluvicto for prostate cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This achievement has shed light on the potential of targeted radionuclide therapy for other solid tumors, including GBM. This review presents the current status of targeted radionuclide therapy in GBM, highlighting the commonly used therapeutic radionuclides emitting alpha, beta particles, and Auger electrons that could induce potent molecular and cellular damage to treat GBM. We then explore a range of targeting vectors, including small molecules, peptides, and antibodies, which selectively target antigen-expressing tumor cells with minimal or no binding to healthy tissues. Considering that radiopharmaceuticals for GBM are often administered locoregionally to bypass the blood-brain barrier (BBB), we review prominent delivery methods such as convection-enhanced delivery, local implantation, and stereotactic injections. Finally, we address the challenges of this therapeutic approach for GBM and propose potential solutions.

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Section: Trt Applications For Gbmmentioning

confidence: 91%

Targeted Radionuclide Therapy in Glioblastoma

Zhao,

Jakobsson,

Tao

et al. 2024

ACS Appl. Mater. Interfaces

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“…Bevacizumab, a monoclonal antibody against human vascular endothelial growth factor, can improve focal neurologic symptoms and quality of life in a subset of patients (usually with large, necrotic enhancing tumors) and reduce the chronic burden of corticosteroid therapy. 53 The drug is given with various dosing regimens IV, usually once every 2 to 3 weeks. Interestingly, radiologic response to bevacizumab is much more common than clinical improvement, but such “pseudoresponse” should not justify ongoing therapy unless significant clinical improvement occurs (usually within three doses), due to the ongoing risks of DVT and other serious complications.…”

Section: Prognosismentioning

confidence: 99%

Neuro-oncology Treatment Strategies for Primary Glial Tumors

Santos-Pinheiro,

Graber

2023

Semin Neurol

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Primary brain tumors underwent reclassification in the 2021 World Health Organization update, relying on molecular findings (especially isocitrate dehydrogenase mutations and chromosomal changes in 1p, 19q, gain of chromosome 7 and loss of chromosome 10). Newer entities have also been described including histone 3 mutant midline gliomas. These updated pathologic classifications improve prognostication and reliable diagnosis, but may confuse interpretation of prior clinical trials and require reclassification of patients diagnosed in the past. For patients over seventy, multiple studies have now confirmed the utility of shorter courses of radiation, and the risk of post-operative delirium. Ongoing studies are comparing proton to photon radiation. Long term follow up of prior clinical trials have confirmed the roles and length of chemotherapy (mainly temozolomide) in different tumors, as well as the wearable novottf device. New oral isocitrate dehydrogenase inhibitors have also shown efficacy in clinical trials.

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“…Several studies have also indicated the use of inhibitors for the epidermal growth factor receptor (EGFR) due to the strong involvement of the downstream PI3K/Akt pathway in glioma cell proliferation [7,8]. However, resistance against temozolomide and the toxicity of bevacizumab have been documented [9,10], while EGFR inhibitors tend to struggle in penetrating the blood-brain barrier [11]. Hence, the poor prognosis of the five-year survival rate of patients with GBM has not improved significantly despite sustained efforts [12,13].…”

Section: Introductionmentioning

confidence: 99%

Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades

Orda,

Fowler,

Tayo

2024

Biology

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Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance to treatment strategies. In this work, the key hub genes mainly associated with different grades of glioma, which were represented by pilocytic astrocytoma (PA), oligodendroglioma (OG), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM), were identified through weighted gene co-expression network analysis (WGCNA) of microarray datasets retrieved from the Gene Expression Omnibus (GEO) database. Through this, four highly correlated modules were observed to be present across the PA (GSE50161), OG (GSE4290), AA (GSE43378), and GBM (GSE36245) datasets. The functional annotation and pathway enrichment analysis done through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that the modules and hub genes identified were mainly involved in signal transduction, transcription regulation, and protein binding, which collectively deregulate several signaling pathways, mainly PI3K/Akt and metabolic pathways. The involvement of several hub genes primarily linked to other signaling pathways, including the cAMP, MAPK/ERK, Wnt/β-catenin, and calcium signaling pathways, indicates potential interconnectivity and influence on the PI3K/Akt pathway and, subsequently, glioma severity. The Drug Repurposing Encyclopedia (DRE) was used to screen for potential drugs based on the up- and downregulated hub genes, wherein the synthetic progestin hormones norgestimate and ethisterone were the top drug candidates. This shows the potential neuroprotective effect of progesterone against glioma due to its influence on EGFR expression and other signaling pathways. Aside from these, several experimental and approved drug candidates were also identified, which include an adrenergic receptor antagonist, a PPAR-γ receptor agonist, a CDK inhibitor, a sodium channel blocker, a bradykinin receptor antagonist, and a dopamine receptor agonist, which further highlights the gene network as a potential therapeutic avenue for glioma.

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Efficacy and Safety of Bevacizumab for Treating Glioblastoma: A Systematic Review and Meta-Analysis of Phase II and III Randomized Controlled Trials

Cited by 4 publications

References 40 publications

Targeted Radionuclide Therapy in Glioblastoma

Targeted Radionuclide Therapy in Glioblastoma

Neuro-oncology Treatment Strategies for Primary Glial Tumors

Modular Hub Genes in DNA Microarray Suggest Potential Signaling Pathway Interconnectivity in Various Glioma Grades

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