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.
Jordan
Mary Ann
MA
Department of Molecular, Cellular and Developmental Biology, University of California-Santa Barbara, Santa Barbara, CA 93106, USA. jordan@lifesci.ucsb.edu
Horwitz
Susan Band
SB
Lobert
Sharon
S
Correia
John J
JJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle; D016923:Cell Death / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D050257:Tubulin Modulators; C111217:vinflunine; D014747:Vinblastine