title: βIII-Tubulin: biomarker of taxane resistance or drug target?
abstract: BACKGROUND
  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.
  
  
  METHODS
  We reviewed 59 translational studies, including cohorts from lung, ovarian, breast, gastric, colorectal and various miscellaneous cancers subject to different chemotherapy regimens.
  
  
  CONCLUSIONS
  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.
authors: Reproductive Tumor Biology Research, Department of Obstetrics and Gynecology, Danbury Hospital, Biomedical Laboratory, Danbury, CT 06810, USA.
authors: Roshan
authors: R
authors: Karki
authors: Marisa
authors: M
authors: Mariani
authors: Mirko
authors: M
authors: Andreoli
authors: Shiquan
authors: S
authors: He
authors: Giovanni
authors: G
authors: Scambia
authors: Shohreh
authors: S
authors: Shahabi
authors: Cristiano
authors: C
authors: Ferlini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D014404:Tubulin / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D001952:Bridged-Ring Compounds; D009363:Neoplasm Proteins; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; D050257:Tubulin Modulators; C080625:taxane