68P - Inflammatory meditated mechanisms of cisplatin resistance in non-small cell lung cancer

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Kenneth O'Byrne
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. O'Byrne1, S. Ryan2, S. Heavey3, K. Umezawa4, M.P. Barr3, S.G. Gray3, A. Davies5, D. Richard6, K. Gately3, A. Baird2
  • 1Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, QLD 4102 - Brisbane/AU
  • 2Cancer And Ageing Research Program And Translational Cell Imaging Queensland, Queensland University of Technology, Brisbane/AU
  • 3Thoracic Oncology, St James's Hospital, D8 - Dublin/IE
  • 4Dept. Of Molecular Target Medicine Screening, Aichi Medical University, Aichi/JP
  • 5Translational Cell Imaging Queensland, Queensland University of Technology, QLD 4102 - Brisbane/AU
  • 6Institute Of Health And Biomedical Innovation, Cancer And Ageing Research Program, Queensland University of Technology, Brisbane/AU



The majority of non-small cell lung cancer (NSCLC) patients present with advanced stage disease, where chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with cisplatin-based chemotherapy will eventually develop resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project is to determine the role of inflammatory mediators in cisplatin resistance.


A qPCR array was utilised to screen a panel of matched Parental (Cisplatin sensitive) and CisR (Cisplatin resistant) NSCLC cell lines for NFKB and its downstream targets. Through Ingenuity Pathway analysis software, a number of mediators where selected for further study at the gene (qPCR) and protein level (Western Blot/ELISA). Treatment with an NFKB inhibitor, DHMEQ, alone or in combination with cisplatin was also used to determine the effect of blocking NFKB pathways in Parental and CisR cells. The response was characterised in terms of proliferation (BrdU ELISA), viability (Cytell) and the DNA damage response (IR/gammaH2AX/Comet). In addition, the response of Parental and CisR cells to a number of recombinant chemokines was examined in terms of cisplatin sensitivity.


Array studies demonstrated that a number of inflammatory mediators are elevated in the CisR cells compared with Parental cells. Initial results suggest that resistance may be driven through a possible TNF regulated induction of CCL chemokines. Blocking NFKB, led to increased cisplatin efficacy and elevated IR induced DNA damage. In addition, recombinant CCL chemokines provided a protective effect against cisplatin. However, this was overcome by the addition of DHMEQ.


Inflammation may play a critical role in acquired and intrinsic cisplatin resistance. The drug, DHMEQ, may provide a possible means to overcome this resistance and re-sensitise patients to therapy. Given the promising studies arising in the immuno-oncology arena, the immune regulators identified in this project may provide innovative targets for immune mediated therapy in NSCLC.

Clinical trial identification

Legal entity responsible for the study

Queensland University of Technology


Queensland Health


All authors have declared no conflicts of interest.