Strategies to Improve the Killing of Tumors Using Temozolomide: Targeting the DNA Repair Protein MGMT

Authors:
  • LLL. -T. Li
    L. -T. Li
  • YXY. Xin
    Y. Xin
  • LZL. Zhang
    L. Zhang
  • YLY. -Q. Liu
    Y. -Q. Liu
  • JZJ. -N. Zheng
    J. -N. Zheng
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Abstract
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 O6-methylguanine, a cytotoxic DNA lesion. This damage may be repaired by the DNA repair enzyme O6-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.