Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents?

Abstract

On the basis of preclinical studies that show overexpression of class III beta-tubulin is associated with resistance to tubulin-binding agents, several investigators have addressed the relation between class III beta-tubulin and outcome in patients treated with such agents. High expression of class III beta-tubulin has been found to be correlated either with low response rates in patients treated with regimens containing taxanes or vinorelbine or with reduced survival in patients with non-small-cell lung cancer, in breast, ovarian, and gastric cancers, and in cancers of unknown primary site. Two studies have shown patients with advanced non-small-cell lung cancer receiving paclitaxel whose tumours expressed high levels of class III beta-tubulin had a lower response to paclitaxel and shorter survival, whereas this variable was not found to be predictive in patients receiving regimens without tubulin-binding agents. Conversely, analysis of samples from patients in the JBR-10 trial, which compared adjuvant chemotherapy to no further therapy in operable non-small-cell lung cancer, showed that chemotherapy seemed to overcome the negative prognostic effect of high levels of expression of class III beta-tubulin and the greatest benefit from cisplatin/vinorelbine was seen in patients with high levels of expression of class III beta-tubulin. Further analyses in operable and advanced non-small-cell lung cancer showed a relation between high expression of class III beta-tubulin and baseline factors such as age under 60 years, adenocarcinoma and large-cell carcinoma histologies, and advanced stage of disease. These results suggest that class III beta-tubulin could be both a prognostic and a predictive factor. Large randomised studies are warranted to determine the prognostic or predictive value of class III beta-tubulin in different settings and tumours.