Topoisomerase I inhibitors: selectivity and cellular resistance

Citation
Y. Pommier et al., Topoisomerase I inhibitors: selectivity and cellular resistance, DRUG RESIST, 2(5), 1999, pp. 307-318
Citations number
119
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Toxicology
Journal title
DRUG RESISTANCE UPDATES
ISSN journal
1368-7646 → ACNP
Volume
2
Issue
5
Year of publication
1999
Pages
307 - 318
Database
ISI
SICI code
1368-7646(1999)2:5<307:TIISAC>2.0.ZU;2-P
Abstract
Topoisomerase I (top I)inhibitors (camptothecins and other structurally div erse compounds) are effective and promising anticancer agents. Determinants of selectivity toward cancer cells and resistance are multifactorial. Thes e factors can be separated in three groups. The first is related to alterat ions in drug distribution and metabolism. The second group includes both qu antitative and qualitative (mutations) differences in top I. The third grou p includes resistance and sensitivity factors downstream from the cleavage complexes. They include DNA repair, cell cycle checkpoints and apoptosis, a nd are probably key to the relative selectivity of camptothecins toward can cer cells and to clinical resistance.