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

S. L. Gerson, J. K. Willson

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 alkyl-transferase 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 - Apr 1995

Fingerprint

Drug Resistance
Alkylating Agents
Neoplasms
Triazines
Transferases
Heterografts
DNA Repair
Proteins
Drug Therapy
DNA alkyltransferase

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

O6-alkylguanine-DNA alkyltransferase. A target for the modulation of drug resistance. / Gerson, S. L.; Willson, J. K.

In: Hematology/Oncology Clinics of North America, Vol. 9, No. 2, 04.1995, p. 431-450.

Research output: Contribution to journalArticle

@article{70380a3292b145f0936d548325f8b2d8,
title = "O6-alkylguanine-DNA alkyltransferase. A target for the modulation of drug resistance.",
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 alkyl-transferase 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.",
author = "Gerson, {S. L.} and Willson, {J. K.}",
year = "1995",
month = "4",
language = "English (US)",
volume = "9",
pages = "431--450",
journal = "Hematology/Oncology Clinics of North America",
issn = "0889-8588",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - O6-alkylguanine-DNA alkyltransferase. A target for the modulation of drug resistance.

AU - Gerson, S. L.

AU - Willson, J. K.

PY - 1995/4

Y1 - 1995/4

N2 - 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 alkyl-transferase 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.

AB - 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 alkyl-transferase 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.

UR - http://www.scopus.com/inward/record.url?scp=0028987003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028987003&partnerID=8YFLogxK

M3 - Article

C2 - 7642472

AN - SCOPUS:0028987003

VL - 9

SP - 431

EP - 450

JO - Hematology/Oncology Clinics of North America

JF - Hematology/Oncology Clinics of North America

SN - 0889-8588

IS - 2

ER -