Through my doctoral research, I have sought to investigate how taxane efficacy might be improved for the treatment of respiratory tract cancer with a focus on its most prevalent form Non-Small Cell Lung Cancer (NSCLC). In this way, I found that AURKA mRNA over-expression could prognosticate the clinical outcome in NSCLC patients suggesting that patients bearing tumours with high AURKA expression may benefit from the combined use of AURKA inhibitors. My PhD study has also clearly uncovered a role for AURKB in the response of NSCLC cells to paclitaxel and provided unique evidence for a dose-dependent association. Given the large extent of AURKB deregulation in NSCLC, my findings suggest that assessing the levels of AURKB protein in surgical samples could become a determinant in the clinical decision tree for managing patients and have the potential for development as a predictive biomarker. Although preliminary, the data suggest that pre-treatment (but not concurrent treatment) of NSCLC cells with the HDAC inhibitor, valproic acid (VPA) generates a super-additive cytotoxicity when combined with paclitaxel. The effect of VPA appeared to be influenced by p53 mutational status. No cooperation was detected for the methylase inhibitor decitabine.
This work has been performed as part of a collaboration between two of the main research groups in the Department of Molecular & Clinical Cancer Medicine; the Roy Castle Lung Cancer Research Programme and the Mersey Head & Neck Oncology Group, co-located in the University of Liverpool Cancer Research Centre.