Class III b-tubulin overexpression in gynecologic tumors: implications for the choice of microtubule targeted agents?

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.