TY - JOUR
T1 - O6-alkylguanine-DNA alkyltransferase
T2 - A target for the modulation of drug resistance
AU - Gerson, S. L.
AU - Willson, J. K.
PY - 1995
Y1 - 1995
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 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.
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 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.
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U2 - 10.1016/s0889-8588(18)30103-5
DO - 10.1016/s0889-8588(18)30103-5
M3 - Review article
C2 - 7642472
AN - SCOPUS:0028987003
SN - 0889-8588
VL - 9
SP - 431
EP - 450
JO - Hematology/Oncology Clinics of North America
JF - Hematology/Oncology Clinics of North America
IS - 2
ER -