MGMT / AGAT (EP337), RMab

Summary and Explanation

High MGMT antibody expression has been reported in Glioma, Myeloma, Melanoma, Colon and Pancreatic Cancers, where inhibition or down-regulation make alkylating drug treatments more effective. MGMT expression is lost in some cancer types such as Lymphomas, Non-Small Cell Lung Cancer, Astrocyte Tumors, Breast, and Prostate Cancer, where it may fail to prevent mutations. A study detected protein expression of MGMT by IHC and MGMT promoter methylation detected by methylation-specific polymerase chain reaction (MSP) were performed in a series of newly diagnosed Glioblastomas and found that the MGMT status detected by either IHC or MSP was significantly correlated with the treatment response and survival of Glioblastoma patients. MGMT methylation is frequently observed in sporadic colorectal cancer and was recently correlated with the C>T allele at SNP rs16906252, within the transcriptional enhancer element of the promoter. MGMT methylation has also been associated with KRAS mutations, particularly G>A transitions. Another study address the association between sequence variants within the MGMT (O(6)-methylguanine-DNA methyltransferase) promoter-enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targeting MGMT for therapy and found strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, TMZ treatment may benefit a subset of lung cancer patients methylated for MGMT.