Mechanisms of resistance to camptothecins

A. Saleem; T. K. Edwards; Z. Rasheed; E. H. Rubin

doi:10.1111/j.1749-6632.2000.tb07024.x

Mechanisms of resistance to camptothecins

A. Saleem, T. K. Edwards, Z. Rasheed, E. H. Rubin

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) reduced cellular accumulation of camptothecins, (2) alteration in the structure or location of topoisomerase I, and (3) alterations in the cellular response to camptothecin-DNA-ternary complex formation. The relevance of these mechanisms to clinical drug resistance is not yet known, but evaluation of these models in clinical specimens should enhance the use of camptothecins both as single agents and in combination with other anticancer drugs.

Original language	English (US)
Pages (from-to)	46-55
Number of pages	10
Journal	Annals of the New York Academy of Sciences
Volume	922
DOIs	https://doi.org/10.1111/j.1749-6632.2000.tb07024.x
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
History and Philosophy of Science

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10.1111/j.1749-6632.2000.tb07024.x

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title = "Mechanisms of resistance to camptothecins",

abstract = "Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) reduced cellular accumulation of camptothecins, (2) alteration in the structure or location of topoisomerase I, and (3) alterations in the cellular response to camptothecin-DNA-ternary complex formation. The relevance of these mechanisms to clinical drug resistance is not yet known, but evaluation of these models in clinical specimens should enhance the use of camptothecins both as single agents and in combination with other anticancer drugs.",

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AU - Saleem, A.

AU - Edwards, T. K.

AU - Rasheed, Z.

AU - Rubin, E. H.

PY - 2000

Y1 - 2000

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AB - Camptothecins are broad-spectrum anticancer drugs that specifically target DNA topoisomerase I. Although the availability of camptothecins has had a significant impact on cancer therapeutics, de novo or acquired clinical resistance to camptothecins is common. Studies of camptothecin resistance using yeast and mammalian cell culture models suggest three general mechanisms of resistance: (1) reduced cellular accumulation of camptothecins, (2) alteration in the structure or location of topoisomerase I, and (3) alterations in the cellular response to camptothecin-DNA-ternary complex formation. The relevance of these mechanisms to clinical drug resistance is not yet known, but evaluation of these models in clinical specimens should enhance the use of camptothecins both as single agents and in combination with other anticancer drugs.

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Mechanisms of resistance to camptothecins

Abstract

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