The prognostic value of MGMT promoter methylation in glioblastoma: A meta‐analysis of clinical trials

Binabaj, Maryam Moradi; Bahrami, Afsane; Shahidsales, Soodabeh; Joodi, Marjan; Mashhad, Mona Joudi; Hassanian, Seyed Mahdi; Anvari, Kazem

doi:10.1002/jcp.25896

Cited by 259 publications

(202 citation statements)

References 47 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…This feature was associated with a better overall survival, 21.7 months after chemotherapy associated with radiotherapy, in comparison to 15.3 months for patients carrying non-methylated genotype (Stupp et al, 2009). More recently, a meta-analysis of 10 eligible studies, including the MGMT methylation status of more than four thousand subjects, confirmed that patients bearing this genotype present longer overall survival (Binabaj et al, 2018), emphasizing MGMT status as an independent indicator of a favorable prognosis. MGMT methylation could also be found in patient serum and strongly correlated with its presence in the tumor tissues (Fiano et al, 2014), suggesting that detection in blood samples could represent a re-DNA repair genes in astrocytoma 3 liable tool to predict response to TMZ treatment.…”

Section: Dna Repair Genes As Biomarkers Of Astrocytoma Aggressivenessmentioning

confidence: 91%

See 1 more Smart Citation

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

et al. 2020

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, showing rapid development and resistance to therapies. On average, patients survive 14.6 months after diagnosis and less than 5% survive five years or more. Several pieces of evidence have suggested that the DNA damage signaling and repair activities are directly correlated with GBM phenotype and exhibit opposite functions in cancer establishment and progression. The functions of these pathways appear to present a dual role in tumorigenesis and cancer progression. Activation and/or overexpression of ATRX, ATM and RAD51 genes were extensively characterized as barriers for GBM initiation, but paradoxically the exacerbated activity of these genes was further associated with cancer progression to more aggressive stages. Excessive amounts of other DNA repair proteins, namely HJURP, EXO1, NEIL3, BRCA2, and BRIP, have also been connected to proliferative competence, resistance and poor prognosis. This scenario suggests that these networks help tumor cells to manage replicative stress and treatment-induced damage, diminishing genome instability and conferring therapy resistance. Finally, in this review we address promising new drugs and therapeutic approaches with potential to improve patient survival. However, despite all technological advances, the prognosis is still dismal and further research is needed to dissect such complex mechanisms.

show abstract

Section: Dna Repair Genes As Biomarkers Of Astrocytoma Aggressivenessmentioning

confidence: 91%

“…DNA repair genes considered biomarkers* of GBM susceptility and/or progression Hegi et al, 2005;Hegi et al, 2008;Stupp et al, 2009;Binabaj et al, 2018. …”

mentioning

confidence: 99%

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Thus, increased MGMT activity in tumour cells counteracts the cytotoxic damage induced by antitumour agents [10]. Since the initial research by Esteller et al [11], many studies have provided convincing evidence showing that glioma patients with decreased level of MGMT activity have longer overall survival (OS) and progression-free survival (reviewed in [12]). The decrease of MGMT activity in glioma cells is caused by epigenetic silencing of MGMT through hypermethylation of cytidine-phosphate-guanosine dinucleotides (CpG islands) in the promoter region, rather than mutations or deletions.…”

Section: Introductionmentioning

confidence: 99%

“…The decrease of MGMT activity in glioma cells is caused by epigenetic silencing of MGMT through hypermethylation of cytidine-phosphate-guanosine dinucleotides (CpG islands) in the promoter region, rather than mutations or deletions. These findings led to the suggestion that the MGMT promoter methylation status could serve as a highly promising prognostic factor for malignant glioma patients [12,13]. However, several studies dealing with the MGMT methylation status in malignant glioma gave controversial results suggesting that the prognostic value of MGMT promoter methylation on GBM remains unclear [12,[14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of MGMT promoter methylation in diffuse glioma patients

Jovanović

Mitrović

Cvetković

et al. 2019

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidinephosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers. ARTICLE HISTORY

show abstract

“…MGMT is a suicide repair protein which removes the O6-guanine adduct and allows for proper DNA repair 6 . Even with this information, targeting MGMT with both small molecule drugs and mimetics has been unsuccessful, and its expression does not always correlate with resistance to TMZ [7][8][9][10][11] . Therefore, new models of resistance need to be developed in order to better define molecular mechanisms of GBM resistance to TMZ.…”

Section: Introductionmentioning

confidence: 99%

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Tiek

Rone

Graham

et al. 2017

Preprint

View full text Add to dashboard Cite

Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the "go" (8MGBA-TMZres) or "grow" (42MGBA-TMZres) hypothesis of GBM behavior. These model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a

show abstract

The prognostic value of MGMT promoter methylation in glioblastoma: A meta‐analysis of clinical trials

Cited by 259 publications

References 47 publications

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

Prognostic significance of MGMT promoter methylation in diffuse glioma patients

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Contact Info

Product

Resources

About