Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
Chapter 2 - University of British Columbia
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While overall therapeutic strategies have provided limited benefit to prolonging patient survival,<br />
there has been moderate success in the application <strong>of</strong> targeted therapeutics. Specifically,<br />
pharmacological agents against the epidermal growth factor receptor (EGFR) tyrosine kinase<br />
have shown selective efficacy in a subset <strong>of</strong> lung AC patients [6-12]. Hence, in addition to<br />
improving early detection strategies, another main focus <strong>of</strong> lung cancer research is the<br />
identification <strong>of</strong> novel therapeutic targets. One such approach that can be used to identify<br />
targets is through the application <strong>of</strong> genomic tools to clinical lung cancer specimens.<br />
1.2 Genomic pr<strong>of</strong>iling <strong>of</strong> lung cancer<br />
1.2.1 Gene expression analysis<br />
One <strong>of</strong> the first applications <strong>of</strong> high throughput genome technologies was to the assessment <strong>of</strong><br />
messenger RNA (mRNA) levels [13, 14]. While the first, landmark cancer-related studies were<br />
done in breast and hematological malignancies [15-17], substantial findings were made in the<br />
analysis <strong>of</strong> lung cancer. Specifically, lung cancer gene expression studies have identified<br />
genes differentially expressed in tumors, genes associated with angiogenic potential, genes<br />
associated with chemoresistance, expression signatures defining subclasses <strong>of</strong> lung cancer,<br />
expression signatures associated with patient prognosis, and expression signatures from<br />
normal bronchial epithelium samples to detect lung cancer [18-34]. In addition, much work has<br />
also been done to understand baseline gene expression in non-malignant lung tissue as well its<br />
changes with respect to heavy smoke exposure [35-38]. These studies are as important as<br />
studies involving lung cancer samples as they provide an important reference level <strong>of</strong> gene<br />
expression to decipher the dysregulated gene expression in tumors.<br />
However, from a given analysis <strong>of</strong> differential expression in tumors, there are typically<br />
hundreds, if not thousands, <strong>of</strong> genes which may show aberrant gene expression in tumors when<br />
compared to non-malignant tissue. Moreover, it is likely that a proportion <strong>of</strong> the genes which<br />
are aberrantly expressed are not integral or causal to tumor development as many gene<br />
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