Potential mechanisms of resistance to microtubule inhibitors.
Antimitotic drugs targeting the microtubules, such as the taxanes and vinca alkaloids, are widely used in the treatment of neoplastic diseases. Development of drug resistance over time, however, limits the efficacy of these agents and poses a clinical challenge to long-term improvement of patient outcomes. Understanding the mechanism(s) of drug resistance becomes paramount to allowing for alternative, if not improved, therapeutic options that might circumvent this challenge. Vinflunine, a novel microtubule inhibitor, has shown superior preclinical antitumor activity, and displays a different pattern of resistance, compared with other agents in the vinca alkaloid class.
Kavallaris
Maria
M
Children's Cancer Institute Australia for Medical Research, High Street, 2031 Randwick, NSW, Australia.
Annereau
Jean-Philippe
JP
Barret
Jean-Marc
JM
D000199:Actins / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D014404:Tubulin / Q000235:genetics; D050257:Tubulin Modulators / Q000627:therapeutic use*; D014747:Vinblastine / Q000031:analogs & derivatives*; D014748:Vinca Alkaloids / Q000494:pharmacology
D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014404:Tubulin; D050257:Tubulin Modulators; D014747:Vinblastine; D014748:Vinca Alkaloids