Novel microtubule-targeting agents – the epothilones
Kit L Cheng, Thomas Bradley, Daniel R Budman1Monter Cancer Center, North Shore – LIJ Health Systems, Lake Success, New York, USAAbstract: Epothilones are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from taxanes and are more...
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Dove Medical Press
2008
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oai:doaj.org-article:72e05137839c4d13b14316ea5a51b0462021-12-02T07:40:55ZNovel microtubule-targeting agents – the epothilones1177-54751177-5491https://doaj.org/article/72e05137839c4d13b14316ea5a51b0462008-10-01T00:00:00Zhttp://www.dovepress.com/novel-microtubule-targeting-agents-ndash-the-epothilones-a2493https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Kit L Cheng, Thomas Bradley, Daniel R Budman1Monter Cancer Center, North Shore – LIJ Health Systems, Lake Success, New York, USAAbstract: Epothilones are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from taxanes and are more amenable to synthetic modification. Six epothilones have been studied in preclinical and clinical trials: patupilone (epothilone B), ixabepilone (BMS247550), BMS 310705, sagopilone (ZK-EPO), KOS-862 (epothilone D), and KOS-1584. In vitro data have shown increased potency in taxane-sensitive and taxane-resistant cancer cell lines. This enhanced cytotoxic effect has been attributed to epothilone being a poor substrate for p-glycoprotein drug resistance protein and having high affinity to the various β tubulin isoforms. Phase I clinical data have shown different dose-limiting toxicities for each of the epothilones. These effects are drug specific, dose specific, and schedule of administration specific. While diarrhea and myelosuppression are the dose-limiting toxicities for patupilone and BMS 310705, respectively, neurologic toxicity, as seen with taxanes, is the dose-limiting toxicity of ixabepilone, sagopilone, and KOS-862. In an effort to decrease neurologic toxicity, investigators have modified dosing schedules with limited success. Ixabepilone has the most mature clinical results with published phase II and III data, and regulatory approval for clinical use in the treatment of breast cancer. Ixabepilone has also been combined with other anticancer agents and has regulatory approval in combination with capecitabine for heavily treated breast cancer.Keywords: microtubule-targeting agents, epothilones, taxanes, ixabepilone Daniel R BudmanThomas BradleyKit L ChengDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 4, Pp 789-811 (2008) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Daniel R Budman Thomas Bradley Kit L Cheng Novel microtubule-targeting agents – the epothilones |
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Kit L Cheng, Thomas Bradley, Daniel R Budman1Monter Cancer Center, North Shore – LIJ Health Systems, Lake Success, New York, USAAbstract: Epothilones are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from taxanes and are more amenable to synthetic modification. Six epothilones have been studied in preclinical and clinical trials: patupilone (epothilone B), ixabepilone (BMS247550), BMS 310705, sagopilone (ZK-EPO), KOS-862 (epothilone D), and KOS-1584. In vitro data have shown increased potency in taxane-sensitive and taxane-resistant cancer cell lines. This enhanced cytotoxic effect has been attributed to epothilone being a poor substrate for p-glycoprotein drug resistance protein and having high affinity to the various β tubulin isoforms. Phase I clinical data have shown different dose-limiting toxicities for each of the epothilones. These effects are drug specific, dose specific, and schedule of administration specific. While diarrhea and myelosuppression are the dose-limiting toxicities for patupilone and BMS 310705, respectively, neurologic toxicity, as seen with taxanes, is the dose-limiting toxicity of ixabepilone, sagopilone, and KOS-862. In an effort to decrease neurologic toxicity, investigators have modified dosing schedules with limited success. Ixabepilone has the most mature clinical results with published phase II and III data, and regulatory approval for clinical use in the treatment of breast cancer. Ixabepilone has also been combined with other anticancer agents and has regulatory approval in combination with capecitabine for heavily treated breast cancer.Keywords: microtubule-targeting agents, epothilones, taxanes, ixabepilone |
| format |
article |
| author |
Daniel R Budman Thomas Bradley Kit L Cheng |
| author_facet |
Daniel R Budman Thomas Bradley Kit L Cheng |
| author_sort |
Daniel R Budman |
| title |
Novel microtubule-targeting agents – the epothilones |
| title_short |
Novel microtubule-targeting agents – the epothilones |
| title_full |
Novel microtubule-targeting agents – the epothilones |
| title_fullStr |
Novel microtubule-targeting agents – the epothilones |
| title_full_unstemmed |
Novel microtubule-targeting agents – the epothilones |
| title_sort |
novel microtubule-targeting agents – the epothilones |
| publisher |
Dove Medical Press |
| publishDate |
2008 |
| url |
https://doaj.org/article/72e05137839c4d13b14316ea5a51b046 |
| work_keys_str_mv |
AT danielrbudman novelmicrotubuletargetingagentsampndashtheepothilones AT thomasbradley novelmicrotubuletargetingagentsampndashtheepothilones AT kitlcheng novelmicrotubuletargetingagentsampndashtheepothilones |
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