Strategies to improve the killing of tumors using temozolomide: targeting the DNA repair protein MGMT

• Published in: Current medicinal chemistry Vol. 19; no. 23; p. 3886
• Main Authors: Jiang, G, Li, L-T, Xin, Y, Zhang, L, Liu, Y-Q, Zheng, J-N
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-08-2012
• Subjects: Antineoplastic Agents, Alkylating - pharmacology; Antineoplastic Agents, Alkylating - therapeutic use; Apoptosis - drug effects; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Dacarbazine - therapeutic use; DNA Repair; Drug Resistance, Neoplasm - drug effects; Humans; Neoplasms - drug therapy; O-Methylguanine-DNA Methyltransferase - antagonists & inhibitors; O-Methylguanine-DNA Methyltransferase - genetics; O-Methylguanine-DNA Methyltransferase - metabolism; Oncolytic Viruses - genetics; Oncolytic Viruses - metabolism; RNA Interference; Temozolomide
• ISSN: 1875-533X
• DOI: 10.2174/092986712802002446

Alkylating agents such as temozolomide (TMZ) are effective anticancer drugs for treating a variety of solid tumors including melanoma, glioma, and astrocytoma. TMZ exerts its effects mainly via the mutagenic product O(6)-methylguanine, a cytotoxic DNA lesion. This damage may be repaired by the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT), a key player in the resistance of cancers to TMZ. Several strategies are presently being pursued to improve the killing of tumor cells by TMZ, with inhibition of MGMT being the most promising. In this review, we provide an overview of recent advances in this field.