Microtubule dynamics as a target in oncology.
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.
Risinger
April L
AL
Department of Pharmacology, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Giles
Francis J
FJ
Mooberry
Susan L
SL
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
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