Dr. Grimm on the Brain Cancer Predictive Marker MGMT

Sean Grimm, MD, Assistant Professor, Neurology, Northwestern University, Feinberg School of Medicine, describes using O(6)-methylguanine-DNA methyltransferase (MGMT) as a temozolomide (Temodar) predictive marker for patients with brain tumors. Tumors with high levels of MGMT are resistant to alkylating chemotherapy while low levels are susceptible.

Accurate prediction using MGMT requires the consideration of the promoter gene's methylation. Retrospective studies found that methylated MGMT correlated to lower levels of the MGMT enzyme and were more responsive to temozolomide than non-methylated. Radiation therapy also showed improved efficacy in methylated MGMT patients.

The broad response demonstrated by methylated MGMT may indicate the gene is more than a predictive marker for temozolomide but may be a marker of overall response to treatment.