The role of βIII tubulin in predicting chemoresistance in non-small cell lung cancer

Abstract 

Lung cancer is a leading cause of death among adults. Non-small cell lung cancer (NSCLC) accounts for ∼85% of all lung cancer cases. For more than half of all patients diagnosis does not occur until the disease has metastasised. At this advanced stage, the 5-year survival rate is just 15%. Platinum-based chemotherapy forms the backbone of treatment for patients with advanced NSCLC and forms an important component of the therapeutic regimen for many patients with earlier stage disease. However, although a number of agents are available to partner the platinum-based compounds, treatment selection is largely empiric, and chemoresistance is a considerable barrier to improving outcomes. The identification of biologic and other markers to guide treatment selection, thus ensuring patients receive the most effective regimen for their individual tumour and avoid exposure to toxic agents from which they are unlikely to benefit, will be critical to improve outcomes for patients with NSCLC. The development of alternative agents for those patients who express predictors of a negative clinical response is of vital importance. A variety of biomarkers are emerging, including expression of DNA repair enzymes, ribonucleotide subunits and βIII tubulin. Treatment algorithms based on elucidation of such markers to guide treatment selection can already be envisaged. For example, those patients with high βIII tubulin expression should be considered for epothilone therapy as an alternative to taxane-based regimens. The epothilones may be preferred option as the evidence suggests that these agents retain activity versus taxane-resistant cancers. This paper reviews the evidence base for βIII tubulin expression as a prognostic and predictive biomarker in NSCLC and briefly explores the implications for clinical decision making of this and other emerging biomarkers.

Keywords: Non-small cell lung cancer, Biomarker, Tubulin, ERCC1, RRM1, Tubulin-binding agent, Taxane, Epothilone