The role of O-6 methylguanine DNA methyltransferase (MGMT) in drug resistance and strategies for its inhibition.

Abstract:

:The marginal level of clinical responses to the Chloroethylnitrosoureas (CENU, i.e. BCNU, CCNU, MeCCNU) suggests that there may exist an innate mechanism of resistance in tumors to these chemotherapeutic agents. A decade of research from many laboratories around the world has led to the identification of the mechanisms for tumor cell resistance to the CENU. The ability to prevent the formation of DNA interstrand crosslinks, thought to be the critical lethal lesion induced by these agents, is accomplished in a majority of human tumors by the unique DNA repair protein O-6 methylguanine DNA methyltransferase (MGMT). This review addresses the identification of this mechanism of resistance to therapy, and chemotherapeutic strategies to inhibit this DNA repair system, in an attempt to sensitize resistant tumors to the CENU.

journal_name

Semin Cancer Biol

authors

Erickson LC

subject

Has Abstract

pub_date

1991-08-01 00:00:00

pages

257-65

issue

4

eissn

1044-579X

issn

1096-3650

journal_volume

2

pub_type

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