βIII-Tubulin: Biomarker of taxane resistance or drug target?

Roshan Karki, Marisa Mariani, Mirko Andreoli, Shiquan He, Giovanni Scambia, Shohreh Shahabi, Cristiano Ferlini*

*Corresponding author for this work

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

Introduction: βIII-Tubulin (TUBB3) is predominantly expressed in neurons of the central and peripheral nervous systems, while in normal non-neoplastic tissues it is barely detectable. By contrast, this cytoskeletal protein is abundant in a wide range of tumors. βIII-Tubulin is linked to dynamic instability of microtubules (MTs), weakening the effects of agents interfering with MT polymerization. Based on this principle, early studies introduced the classical theory linking βIII-tubulin with a mechanism of counteracting taxane activity and accordingly, prompted its investigation as a predictive biomarker of taxane resistance. Areas covered: We reviewed 59 translational studies, including cohorts from lung, ovarian, breast, gastric, colorectal and various miscellaneous cancers subject to different chemotherapy regimens. Expert opinion: βIII-Tubulin functions more as a prognostic factor than as a predictor of response to chemotherapy. We believe this view can be explained by βIII-tubulin's association with prosurvival pathways in the early steps of the metastatic process. Its prognostic response increases if combined with additional biomarkers that regulate its expression, since βIII-tubulin can be expressed in conditions, such as estrogen exposure, unrelated to survival mechanisms and without any predictive activity. Additional avenues for therapeutic intervention could emerge if drugs are designed to directly target βIII-tubulin and its mechanism of regulation.

Original languageEnglish (US)
Pages (from-to)461-472
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Biomarker
  • Cancer
  • Chemotherapy
  • Docetaxel
  • Drug resistance
  • Microtubules
  • Paclitaxel
  • TUBB3
  • Taxanes
  • Therapeutics
  • Translational studies
  • Vinorelbine
  • βIII-tubulin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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