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Targeted Modulation of MGMT: Clinical Implications

Authors' Affiliation: Department of Medicine, Division of Hematology/Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio

Requests for reprints: Stanton L. Gerson, Department of Medicine, Division of Hematology/Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH. Phone: 216-844-8562; Fax: 216-844-4975; E-mail: slg5{at}case.edu.

O⁶-Methylguanine DNA methyltransferase (MGMT) has been studied for >20 years as a gene that is associated with the mutagenicity and cytotoxicity induced by either methylating carcinogens or alkylating (methylating and chloroethylating) therapeutic agents. Pioneering studies of alkylating agents identified alkylated guanine at the O⁶ position, the substrate of MGMT, as a potentially promutagenic and lethal toxic DNA lesion. MGMT plays a prominent role in DNA adduct repair that limits the mutagenic and cytotoxic effect of alkylating agents. Because of its role in cancer etiology and chemotherapy resistance, MGMT is of particular interest. In this article, the clinical effect of MGMT expression and targeted modulation of MGMT will be summarized.

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