A novel approach to overcome temozolomide resistance in glioma and melanoma: Inactivation of MGMT by gene therapy

Biochem Biophys Res Commun. 2011 Mar 18;406(3):311-4. doi: 10.1016/j.bbrc.2011.02.042. Epub 2011 Feb 15.

Abstract

Malignant glioma is the most common primary brain tumor. Malignant melanoma is the most malignant of skin tumor. The two malignancies are poorly responsive to conventional treatment regimens such as chemotherapy. Temozolomide (TMZ) is a DNA-alkylating agent used for the treatment of glioma, astrocytoma, and melanoma. Resistance to alkylating agents such as TMZ correlates with increased expression of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Several studies in animal models have demonstrated that decreasing MGMT level with gene therapy could overcome TMZ resistance and enhance tumor cell death. In the present review, we provide an overview of recent advances in this field.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • DNA Modification Methylases / antagonists & inhibitors*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / antagonists & inhibitors*
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Gene Silencing
  • Genetic Therapy / methods*
  • Glioma / drug therapy*
  • Glioma / enzymology
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / enzymology
  • Temozolomide
  • Tumor Suppressor Proteins / antagonists & inhibitors*
  • Tumor Suppressor Proteins / genetics

Substances

  • Antineoplastic Agents, Alkylating
  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide