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
Cytotechnologyjournal_title
Cytotechnologyauthors
Damia G,D'Incalci Mdoi
10.1023/A:1008060720608subject
Has Abstractpub_date
1998-09-01 00:00:00pages
165-73issue
1-3eissn
0920-9069issn
1573-0778journal_volume
27pub_type
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