ACTR-50. CLINICAL TRIALS WITH DIANHYDROGALACTITOL (VAL-083) IN MGMT-UNMETHYLATED GLIOBLASTOMA

Long-term survival with unmethylated MGMT glioblastoma multiforme

Introduction: Glioblastoma multiforme is the most aggressive tumor of the central nervous system. Despite advances in its management, overall prognosis remains poor, with a median survival time of less than one year. Good response to chemotherapy with temozolomide (TMZ) is usually associated with methylation of the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Case Repor...

Treatment considerations for MGMT-unmethylated glioblastoma. - PubMed - NCBI

Abstract Prognosis for patients with glioblastoma continues to be limited, despite an aggressive, multimodal treatment including alkylating chemotherapy. Temozolomide, the most widely used alkylating agent in glioblastoma, is cytotoxic to cells by inducing DNA damage but can be rapidly repaired by the protein O (6)-methylguanine DNA methyltransferase (MGMT). In a subset of glioblastomas, the MG...

Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.

Resistance to alkylating agents via direct DNA repair by O(6)-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expr...

Homogeneous MGMT Immunoreactivity Correlates with an Unmethylated MGMT Promoter Status in Brain Metastases of Various Solid Tumors

The O(6)-methylguanine-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical reports on treating brain metastases with temozolomide describe varying effects. This may be due to the fact that MGMT promoter methylation of brain metastases has not yet been explored in depth. The...

Clinical Trials in Glioblastoma — Designs and Challenges