MGMT (O6-methylguanine-DNA methyltransferase)
MGMT is a DNA repair enzyme that removes the damage temozolomide causes; when the gene is switched off by methylation the tumour cannot repair itself and the drug works better.
Overview
MGMT is a suicide enzyme that transfers alkyl groups off the O6 position of guanine onto itself, reversing the lesion that temozolomide and nitrosoureas rely on. Promoter methylation silences the gene in about 40 percent of glioblastomas and predicts longer survival with temozolomide; the readout page under this target carries the test methods and the trials that use methylation to select or spare chemotherapy.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · MGMT is a DNA repair enzyme that removes the damage temozolomide causes; when the gene is switched off by methylation the tumour cannot repair itself and the drug works better.
- 1 · What it is
MGMT is a DNA repair enzyme that removes the damage temozolomide causes; when the gene is switched off by methylation the tumour cannot repair itself and the drug works better.
- 2 · What goes wrong in cancer
Loss of MGMT leaves O6-methylguanine unrepaired, which mispairs with thymine and triggers mismatch-repair-driven cell death; tumours that lose mismatch repair as well become hypermutated and resistant.
- 3 · How drugs use it
No product in this corpus aims at MGMT (O6-methylguanine-DNA methyltransferase) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Biology
Loss of MGMT leaves O6-methylguanine unrepaired, which mispairs with thymine and triggers mismatch-repair-driven cell death; tumours that lose mismatch repair as well become hypermutated and resistant.
- Glioblastoma (promoter methylation in about 40 percent)
- Lower-grade gliomas
- Neuroendocrine tumours (low MGMT expression and alkylator response)
Latest papers
topQuery for this target: (TITLE:"MGMT" OR ABSTRACT:"MGMT" OR TITLE:"O6-methylguanine-DNA methyltransferase" OR ABSTRACT:"O6-methylguanine-DNA methyltransferase" OR TITLE:"O-6-methylguanine-DNA methyltransferase" OR ABSTRACT:"O-6-methylguanine-DNA methyltransferase" OR TITLE:"AGT" OR ABSTRACT:"AGT" OR TITLE:"O6-alkylguanine DNA alkyltransferase" OR ABSTRACT:"O6-alkylguanine DNA alkyltransferase") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MGMT (O6-methylguanine-DNA methyltransferase), not a curated reading list.
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