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BIOMARKER:

MGMT overexpression

i
Other names: MGMT, Methylated-DNA--protein-cysteine methyltransferase, 6-O-methylguanine-DNA methyltransferase, O-6-methylguanine-DNA-alkyltransferase
Entrez ID:
Related biomarkers:
Associations
Trials
3d
Genetic polymorphisms, methylation, and expression levels in the GSTP1 and MGMT genes in urothelial bladder tumors. (PubMed, Gene)
In our cohort, MGMT expression seems helpful as a biomarker of good prognosis (low-grade and absence of muscle invasion). A heterogeneous methylation pattern in the MGMT gene requires additional investigation to elucidate its potential implications.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase) • GSTP1 (Glutathione S-transferase pi 1)
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GSTP1 overexpression • MGMT expression • MGMT overexpression
8ms
USP19 regulates DNA methylation damage repair and confers temozolomide resistance through MGMT stabilization. (PubMed, CNS Neurosci Ther)
The regulation of MGMT ubiquitination by USP19 plays a critical role in DNA methylation damage repair and GBM patients' temozolomide chemotherapy response.
Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT expression • MGMT overexpression
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temozolomide
1year
Epigenetic downregulation of O-methylguanine-DNA methyltransferase contributes to chronic hexavalent chromium exposure-caused genotoxic effect and cell transformation. (PubMed, Environ Pollut)
It was further determined that chronic low dose of Cr(VI) exposure-transformed BEAS-2B cells display impaired DNA damage repair capacity and a high sensitivity to the toxicity of the alkylating chemotherapeutic drug Temozolomide...Further mechanistical studies revealed that chronic low dose of Cr(VI) exposure down-regulates MGMT expression through epigenetic mechanisms by increasing DNA methylation and histone H3 repressive modifications. Taken together, these findings suggest that epigenetic down-regulation of a crucial DNA damage repair protein MGMT contributes significantly to the genotoxic effect and cell transformation caused by chronic low dose of Cr(VI) exposure.
Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT expression • MGMT overexpression
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temozolomide
1year
Development of rodent glioblastoma models of MGMT-mediated temozolomide resistance (SNO 2023)
Overall, our newly developed isogenic rat and mouse glioma models recapitulate MGMT-dependent TMZ sensitivity and provide useful preclinical tools for studying MGMT as a biomarker and potential therapeutic target in GBM. In addition, these syngeneic models facilitate studies on the immune modulation of chemotherapeutic agents in the context of MGMT expression and allows for testing of chemoimmunotherapy combinations.
Preclinical • IO biomarker
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT expression • MGMT overexpression
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temozolomide
over1year
Quercetin induces MGMT glioblastoma cells apoptosis via dual inhibition of Wnt3a/β-Catenin and Akt/NF-κB signaling pathways. (PubMed, Phytomedicine)
Our study provides the first evidence that quercetin may induce apoptosis in MGMTGBM cells via dual inhibition of the Wnt3a/β-Catenin pathway and the Akt/NF-κB signaling pathway. These findings suggest that quercetin could be a novel agent for improving GBM treatment, especially in TMZ-resistant GBM with high MGMT expression.
Journal • PARP Biomarker • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • CASP9 (Caspase 9) • ANXA5 (Annexin A5) • WNT3 (Wnt Family Member 3)
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MGMT expression • MGMT overexpression
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temozolomide
over1year
iPSC-Derived Glioblastoma Cells Have Enhanced Stemness Wnt/β-Catenin Activity Which Is Negatively Regulated by Wnt Antagonist sFRP4. (PubMed, Cancers (Basel))
Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/β-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • CD44 (CD44 Molecule) • ABCC2 (ATP Binding Cassette Subfamily C Member 2) • GLI2 (GLI Family Zinc Finger 2) • LEF1 (Lymphoid Enhancer Binding Factor 1) • SFRP4 (Secreted frizzled-related protein 4)
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ABCG2 expression • CD133 expression • CD133 overexpression • GLI2 overexpression • LEF1 overexpression • MGMT expression • MGMT overexpression
almost2years
Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma. (PubMed, Lab Invest)
Reactive oxygen species-mediated DNA damage is at least partially involved. Combinational administration of NCT503 and TMZ may represent a novel and promising treatment strategy to enhance TMZ efficacy in patients with MGMT-high glioblastoma.
Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase) • PHGDH (Phosphoglycerate Dehydrogenase)
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MGMT overexpression
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temozolomide
2years
Role of COL6A2 in malignant progression and temozolomide resistance of glioma. (PubMed, Cell Signal)
COL6A2 high-expression is an indicator for adverse glioma prognosis, and is correlated with TMZ-resistant and immune response. Meanwhile, it may be a prospective biomarker for treatment.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • PD-1 (Programmed cell death 1) • CD276 (CD276 Molecule) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • COL6A2 (Collagen Type VI Alpha 2 Chain)
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HAVCR2 expression • IDO1 expression • IDH wild-type • CTLA4 expression • MGMT overexpression
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temozolomide
over2years
In vitro study of temozolomide resistance in glioma cells (EACR 2022)
Those mechanisms must be evaluated to get a better understanding of the origin of the resistance. These data may support the development of new treatment strategies.
Preclinical
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT overexpression
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temozolomide
over2years
Mannose inhibits proliferation and promotes apoptosis to enhance sensitivity of glioma cells to temozolomide through Wnt/β-catenin signaling pathway. (PubMed, Neurochem Int)
Mannose inhibited MGMT to enhance sensitivity of glioma cells to TMZ, with Wnt/β-catenin pathway involvement. Our data suggested that mannose could be an innovative agent to improve glioma treatment, particularly in TMZ-resistant glioma with high MGMT.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT overexpression
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temozolomide
almost3years
O-methylguanine DNA methyltransferase is upregulated in malignant transformation of gastric epithelial cells via its gene promoter DNA hypomethylation. (PubMed, World J Gastrointest Oncol)
Our finding indicated that MGMT upregulation is induced via its DNA promoter hypomethylation. The highly expressed MGMT prevents the NOCs-induced cell malignant transformation and tumorigenesis, which suggests a potential novel approach for chemical carcinogenesis intervention by regulating aberrant epigenetic mechanisms.
Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT overexpression
3years
Pyrvinium pamoate regulates MGMT expression through suppressing the Wnt/β-catenin signaling pathway to enhance the glioblastoma sensitivity to temozolomide. (PubMed, Cell Death Discov)
The intracranial GBM mouse model also demonstrated that the synergy between PP and TMZ could be achieved through down-regulating β-catenin and MGMT, which prolonged the survival time of tumor-bearing mice. Taken together, our data suggest that PP may serve as the prospect medicine to improve the chemotherapeutic effect on GBM, especially for chemoresistant to TMZ induced by MGMT overexpression.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT overexpression
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temozolomide
3years
Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma. (PubMed, Lab Invest)
Moreover, intracellular levels of reactive oxygen species were elevated especially when NCT503 and TMZ treatments were combined, and the synergistic effects could be partially negated by NAC, a classic scavenger of reactive oxygen species. Taken together, these results suggest that NCT503 may be a promising agent for augmenting TMZ efficacy in the treatment of GBM, especially in TMZ-resistant GBMs with high expression of MGMT.
Clinical • Journal • Epigenetic controller
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MGMT (6-O-methylguanine-DNA methyltransferase) • PHGDH (Phosphoglycerate Dehydrogenase)
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MGMT overexpression
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temozolomide
over3years
Autophagy deficiency downregulates Omethylguanine-DNA methyltransferase and increases chemosensitivity of liver cancer cells. (PubMed, Aging (Albany NY))
Here, we show that autophagy-deficient liver cancer cells exhibit increased DNA damage caused by the chemotherapeutic agent epirubicin...In the absence of autophagy, the chemosensitivity of liver cancer cells was increased, but this was reversed by MGMT overexpression, indicating that autophagy mediates resistance to chemotherapy in liver cancer cells via MGMT. These findings demonstrate a direct link between autophagy, MGMT, and DNA damage repair in liver cancer cells, and show that MGMT not only regulates chemosensitivity to alkylating agents, but may also be involved in other DNA damage repair processes in autophagy-deficient cells.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT overexpression
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epirubicin
over3years
Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours. (PubMed, Endocr Relat Cancer)
We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.
Journal
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ALK (Anaplastic lymphoma kinase) • MGMT (6-O-methylguanine-DNA methyltransferase) • ALK1 (Activin A Receptor Like Type 1)
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MGMT overexpression
almost4years
New genetic prognostic biomarkers in primary central nervous system lymphoma (PCNSL). (PubMed, Brain Behav)
Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • LMO2 (LIM Domain Only 2)
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MYC overexpression • MYC expression • MGMT overexpression