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: Diana P English, Dana M Roque, Alessandro D Santin
• Journal: Expert review of anticancer therapy (Expert Rev Anticancer Ther) Vol. 13 Issue 1 Pg. 63-74 (Jan 2013) ISSN: 1744-8328 [Electronic] England
• PMID: 23259428 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• TUBB3 protein, human
• Tubulin
• Tubulin Modulators

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Genital Neoplasms, Female (drug therapy, genetics, pathology)
• Humans
• Microtubules (metabolism)
• Molecular Targeted Therapy
• Tubulin (genetics)
• Tubulin Modulators (pharmacology)