title: Microtubule dynamics as a target in oncology.
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.
authors.affiliation: Department of Pharmacology, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D003078:Colchicine / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D014748:Vinca Alkaloids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D034261:Epothilones; D007783:Lactones; D018942:Macrolides; D013256:Steroids; D043823:Taxoids; D050257:Tubulin Modulators; D014748:Vinca Alkaloids; C117305:laulimalide; C414085:peloruside A; D003078:Colchicine