Mechanisms of resistance to alkylating agents.

Abstract:

:Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of lethal DNA adducts, and the latter enabling the cell to repair or tolerate the damage. The role in the pre-target mechanisms of reduced drug accumulation and the increased detoxification or activation systems (such as DT-diaphorase, metallothionein, GST/GSH system, etc...) are discussed. In the post-target mechanisms the different DNA repair pathways, tolerance to alkylation damage and the 'downstream' effects (cell cycle arrest and/or apoptosis) are examined.

journal_name

Cytotechnology

journal_title

Cytotechnology

authors

Damia G,D'Incalci M

doi

10.1023/A:1008060720608

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

165-73

issue

1-3

eissn

0920-9069

issn

1573-0778

journal_volume

27

pub_type

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