βIII-tubulin overexpression in cancer: Causes, consequences, and potential therapies

Class III β-tubulin (βIII-tubulin) is frequently overexpressed in human tumors and is associated with resistance to microtubule-targeting agents, tumor aggressiveness, and poor patient outcome. Understanding the mechanisms regulating βIII-tubulin expression and the varied functions βIII-tubulin may have in different cancers is vital to assess the prognostic value of this protein and to develop strategies to enhance therapeutic benefits in βIII-tubulin overexpressing tumors. Here we gather all the available evidence regarding the clinical implications of βIII-tubulin overexpression in cancer, describe factors that regulate βIII-tubulin expression, and discuss current understanding of the mechanisms underlying βIII-tubulin-mediated resistance to microtubule-targeting agents and tumor aggressiveness. Finally, we provide an overview of emerging therapeutic strategies to target tumors that overexpress βIII-tubulin.