Lung cancer is the second most common cancer in men and women (excluding skin cancer) in the US and third most common in Ireland. However, lung cancer is the leading cause of cancer deaths accounting for about 27%. The mortality rates are a reflection of the advanced stage of the disease in which more than 75% of patients present. The poor survival is due to a propensity for early metastasis, the development of chemotherapeutic resistance and heterogeneity (the existence of subpopulations) in tumours which may result in complex interactions and widen the biological capabilities of the tumour. The key to treating lung cancer is the development of diagnostic screening to allow for early detection and to increase our understanding of lung cancer biology to identify more effective treatments.
The DLKP cell line, a poorly differentiated squamous lung carcinoma was isolated and characterised in the NICB. Containing three morphologically distinct subpopulations, with different cancer related properties and having generated a panel of drug resistant variants to a variety of chemotherapeutic drugs, they provide a great resource for studying lung cancer.
The heterogenous nature of the DLKP has revealed subpopulations which exhibit differences in invasiveness and anoikis resistance, two requirements of the metastastic process and combined may allow for a greater metastastic potential. They may also provide a good model for studying the epithelial-mesenchymal transition-like effects that are a frequent feature of cancer.
In addition to metastasis, multiple drug resistance (MDR) occurs where cancer cells overcome the toxic effect not only of the selecting agent but a variety of chemically unrelated therapeutics, altering many pathways and complicating treatments. MDR resistant variants of the DLKP cell line have been developed to a variety of chemotherapeutics and these variants show different levels of resistance with a variety of proteins and pathways differentially regulated in the clones. Current work involves genomic and proteomic investigations to uncover targetable mechanisms underlying resistance and/or metastasis.
Click here to meet our Cancer Research group
- Keenan J, Joyce H, Aherne S, O'Dea S, Doolan P, Lynch V, Clynes M (2012). Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line. Exp Cell Res. Mar 10;318:593-602.
- Keenan J, Murphy L, Henry M, Meleady P and Clynes M (2009). Proteomic analysis of multidrug-resistance mechanisms in adriamycin resistant variants of DLKP, a squamous lung cancer cell line. Proteomics, 2009, 9(6): 1556-66.
- Breen L, Murphy L, Keenan J, Clynes M (2008). Development of taxane resistance in a panel of human lung cancer cell lines. Toxicol In Vitro, 2008, 22(5):1234-41.
- Murphy L, Henry M, Meleady P, Clynes M and Keenan J (2008). Proteomic investigation of taxol and taxotere resistance and invasiveness in squamous lung carcinoma cell line. BBA-proteins and proteomics, 2008, 1784:1184-1191.