Exploring the Mechanisms of Action of the Novel Microtubule Inhibitor Vinflunine
Microtubules have been identified as a suitable target for anticancer therapy, primarily based on their biological importance in coordinating chromosomal segregation at mitosis. Two main classes of microtubule-targeted agents, the taxanes and vinca alkaloids, suppress the dynamic behavior of spindle microtubules, inducing mitotic arrest and subsequent apoptotic cell death. Clinical activity of taxanes and first-generation vinca alkaloids in the treatment of solid tumors and hematologic malignancies, respectively, has prompted further research for novel analogs with improved clinical efficacy and safety. Such efforts have led to the development of vinflunine, a bifluorinated vinca alkaloid endowed with unique antitumor properties. Highlighted in this review are the key features of vinflunine that lead to effective suppression of microtubule dynamics and induction of cell death in cancer cells.
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Dr Jordan has received research support and consulting fees from Bristol-Myers Squibb. Dr Horwitz does not have any financial conflict to report. Dr Lobert has received research support from Pierre Fabre Oncologie and consulting fees from Pierre Fabre Oncologie and Bristol-Myers Squibb. Dr Correia has received research support from Pierre Fabre Oncologie and consulting fees from Pierre Fabre Oncologie, Bristol-Myers Squibb, and Eisai.
PII: S0093-7754(08)00018-3
doi:10.1053/j.seminoncol.2008.01.009
© 2008 Elsevier Inc. All rights reserved.
