Mechanisms of action and resistance to tubulin-binding agents.
Tubulin binding agents constitute an important class of antimitotics and are widely used for the treatment of solid tumours an haematopoietic malignancies. These compounds, currently represented by the vinca alkaloids and the taxanes, differ from most of the other clinically useful antimitotics in that their target is not nucleic acids, but the mitotic spindle, which is an essential component of the mitotic machinery. Recent data on the mechanisms of action of and mechanisms of resistance to tubulin binding agents are presented. The importance of microtubule dynamics is emphasised, in particular in relationship to the usefulness of drug combinations. Concerning the reported resistance mechanisms, an emerging body of data show that altered microtubule structure may be involved in reduced sensitivity to these compounds. Promising new molecules, including those derived from marine organisms are described.
Dumontet
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Service d'Hématologie, Centre Hospitalier Lyon Sud, 69495 Pierre Bénite Cedex, France. charles.dumontet@chu-lyon.fr
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D018432:Drug Resistance, Multiple; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D014714:Vertebrates
D000970:Antineoplastic Agents; D014404:Tubulin