Abstract
Drugs that affect microtubule dynamics, including the taxanes and vinca alkaloids, have been a mainstay in the treatment of leukemias and solid tumors for decades. New, more effective microtubule-targeting agents continue to enter into clinical trials and some, including the epothilone ixapebilone, have been approved for use. In contrast, several other drugs of this class with promising preclinical data were later shown to be ineffective or intolerable in animal models or clinical trials. In this review, we discuss the molecular mechanisms as well as preclinical and clinical results for a variety of microtubule-targeting agents in various stages of development. We also offer a frank discussion of which microtubule-targeting agents are amenable to further development based on their availability, efficacy and toxic profile.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antineoplastic Agents, Phytogenic / therapeutic use
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
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Cell Division / drug effects
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Clinical Trials as Topic
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Colchicine / pharmacology
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Colchicine / therapeutic use
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Drug Delivery Systems*
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Drug Screening Assays, Antitumor
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Epothilones / pharmacology
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Epothilones / therapeutic use
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Humans
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Lactones / pharmacology
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Lactones / therapeutic use
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Macrolides / pharmacology
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Macrolides / therapeutic use
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Microtubules / drug effects*
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Microtubules / physiology
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Microtubules / ultrastructure
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Neoplasms / drug therapy
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Neoplasms / genetics
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Neoplasms / pathology
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Steroids / pharmacology
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Steroids / therapeutic use
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Taxoids / pharmacology
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Taxoids / therapeutic use
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Tubulin Modulators / pharmacology*
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Tubulin Modulators / therapeutic use
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Vinca Alkaloids / pharmacology
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Vinca Alkaloids / therapeutic use
Substances
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Antineoplastic Agents, Phytogenic
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Bridged Bicyclo Compounds, Heterocyclic
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Epothilones
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Lactones
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Macrolides
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Steroids
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Taxoids
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Tubulin Modulators
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Vinca Alkaloids
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laulimalide
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peloruside A
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Colchicine