O6-alkylguanine-DNA alkyltransferase: A target for the modulation of drug resistance

S. L. Gerson, J. K. Willson

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

The DNA repair protein, O6-alkylguanine DNA alkyltransferase, is a major contributor to the resistance to the nitrosourea, triazine, and tetrazine class of alkylating agents. Many tumor cells and primary tumor samples contain high levels of this protein, although a great deal of heterogeneity exists between and within tumors. Inhibition of the alkyltransferase by O6- benzylguanine results in significant potentiation of the cytotoxic effects of these chemotherapeutic agents, generating responses in human tumor xenografts that are completely resistant to nitrosoureas alone. These studies may rekindle the interest in the nitrosourea class of alkylating agents and stimulate the search for inhibitors of other mechanisms of chemotherapy resistance.

Original languageEnglish (US)
Pages (from-to)431-450
Number of pages20
JournalHematology/Oncology Clinics of North America
Volume9
Issue number2
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Hematology
  • Oncology

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