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Mechanisms of resistance to topoisomerase I-targeting drugs.
Oncogene. 2003 Oct 20; 22(47):7296-304.O

Abstract

DNA topoisomerases are a class of enzymes that alter the topology of DNA and are targets of several anticancer drugs. Camptothecins (CPTs) are a relatively new family of compounds that specifically target topoisomerase I (Top1). These compounds "poison" Top1 by binding to the Top1-DNA complex in a manner that prevents the religation of DNA. Topotecan and irinotecan are two CPTs that are approved for the treatment of a variety of malignancies, including colorectal, ovarian, and small cell lung cancers, as well as myeloid malignancies. Although CPTs have proven to be effective anticancer drugs, resistance is still a critical clinical problem. The mechanisms underlying de novo and acquired clinical resistance to CPTs and the newer classes of Top1 poisons are unclear. However, based on preclinical studies, it is likely that clinical resistance to these drugs is the result of: (1) inadequate accumulation of drug in the tumor, (2) resistance-conferring alterations in Top1, or (3) alterations in the cellular response to the Top1-CPT interaction. This review will focus on the current knowledge regarding mechanisms of resistance to CPTs and other Top1-targeting drugs.

Authors+Show Affiliations

The Cancer Institute of New Jersey, Department of Molecular and Cellular Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08901, USA. rasheeze@umdmj.eduNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14576839

Citation

Rasheed, Zeshaan A., and Eric H. Rubin. "Mechanisms of Resistance to Topoisomerase I-targeting Drugs." Oncogene, vol. 22, no. 47, 2003, pp. 7296-304.
Rasheed ZA, Rubin EH. Mechanisms of resistance to topoisomerase I-targeting drugs. Oncogene. 2003;22(47):7296-304.
Rasheed, Z. A., & Rubin, E. H. (2003). Mechanisms of resistance to topoisomerase I-targeting drugs. Oncogene, 22(47), 7296-304.
Rasheed ZA, Rubin EH. Mechanisms of Resistance to Topoisomerase I-targeting Drugs. Oncogene. 2003 Oct 20;22(47):7296-304. PubMed PMID: 14576839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of resistance to topoisomerase I-targeting drugs. AU - Rasheed,Zeshaan A, AU - Rubin,Eric H, PY - 2003/10/25/pubmed PY - 2003/12/3/medline PY - 2003/10/25/entrez SP - 7296 EP - 304 JF - Oncogene JO - Oncogene VL - 22 IS - 47 N2 - DNA topoisomerases are a class of enzymes that alter the topology of DNA and are targets of several anticancer drugs. Camptothecins (CPTs) are a relatively new family of compounds that specifically target topoisomerase I (Top1). These compounds "poison" Top1 by binding to the Top1-DNA complex in a manner that prevents the religation of DNA. Topotecan and irinotecan are two CPTs that are approved for the treatment of a variety of malignancies, including colorectal, ovarian, and small cell lung cancers, as well as myeloid malignancies. Although CPTs have proven to be effective anticancer drugs, resistance is still a critical clinical problem. The mechanisms underlying de novo and acquired clinical resistance to CPTs and the newer classes of Top1 poisons are unclear. However, based on preclinical studies, it is likely that clinical resistance to these drugs is the result of: (1) inadequate accumulation of drug in the tumor, (2) resistance-conferring alterations in Top1, or (3) alterations in the cellular response to the Top1-CPT interaction. This review will focus on the current knowledge regarding mechanisms of resistance to CPTs and other Top1-targeting drugs. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/14576839/Mechanisms_of_resistance_to_topoisomerase_I_targeting_drugs_ L2 - https://doi.org/10.1038/sj.onc.1206935 DB - PRIME DP - Unbound Medicine ER -