title: Class III b-tubulin overexpression in gynecologic tumors: implications for the choice of microtubule targeted agents?
abstract: The tubulins are significant players in maintaining microtubule dynamics and have important signaling and apoptotic functions. Alterations in microtubules as a result of changes in tubulin isotype content or polymerization affect the sensitivity of cell lines to tubulin-binding agents (e.g., taxol) in vitro. Epothilones, such as patupilone and ixabepilone, contain a 16-membered macrolide ring and act as competitive inhibitors of taxol. Class III β-tubulin overexpression has been linked to resistance to paclitaxel and correlated with poor survival in ovarian, breast, gastric, non-small-cell lung cancer and unknown primary tumors. Recent data suggest that class III β-tubulin may not only serve as a marker for sensitivity to epothilones, but also as a mediator of a bioaggressive tumor phenotype through activation of multiple cell survival pathways active under stress conditions.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
authors.forename: Diana P
authors.initials: DP
authors.lastname: English
authors.forename: Dana M
authors.initials: DM
authors.lastname: Roque
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D058990:Molecular Targeted Therapy; D014404:Tubulin / Q000235:genetics*; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C498585:TUBB3 protein, human; D014404:Tubulin; D050257:Tubulin Modulators