Crucial marker for Temozolomide predictive efficacy in GBM.
Promoter methylation Probe
Identify the MGMT status to predict Temozolomide efficacy and tailor adjuvant radiotherapy protocols in high-grade gliomas.
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Prognostication and treatment tailoring following resection or biopsy of a Glioblastoma.
Directly guides adjuvant therapy decisions in elderly patients (>70 years) where combined modality therapy is poorly tolerated.
Section 2
Literature
Development
The significance of O6-methylguanine-DNA methyltransferase (MGMT) was brought to the forefront by Hegi et al. in tandem with the landmark Stupp trial (2005) that established Temozolomide (TMZ) as the standard of care for Glioblastoma. They proved the survival benefit of TMZ was almost entirely concentrated in patients with epigenetically silenced (methylated) MGMT promoters.
Section 3
Formula & Logic
The Futility of TMZ without Methylation
Temozolomide works by attaching alkyl groups to the O6 position of guanine in tumor DNA, preventing replication. If the MGMT enzyme is active (unmethylated promoter), it physically plucks off this alkyl group and repairs the DNA before the cell can trigger apoptosis. If the MGMT promoter is methylated, the gene is silenced, the enzyme is absent, and the DNA damage becomes fatal to the tumor cell.
Section 4
Evidence Appraisal
Primary Reference
MGMT gene silencing and benefit from temozolomide in glioblastoma
Hegi ME et al. • N Engl J Med. 2005;352(10):997-1003
