Background:
Although some success has been achieved in identifying Epidermal growth factor receptor (EGFR) mutations as a molecular predictive marker of response in patients with non-small cell lung cancer (NSCLC), this strategy is likely only to be limited as not all responding patients have a mutation in their tumor and conversely, not all patients with a mutation were responders. Furthermore, as the development of resistance to EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib is inevitable and poses a major clinical problem due to limited therapeutic options, the identification of a molecular profile that could predict sensitivity to erlotinib or gefitinib is warranted.
Hypothesis:
Using serum as an easily accessible biological fluid, we hypothesize that EGFR TKIs modulate tumor changes that may be reflected in the alteration of serum proteins.
Objectives:
* To establish the serum proteomic changes in NSCLC patients receiving erlotinib or gefitinib.
* To identify a serum protein profile that predicts erlotinib or gefitinib sensitivity or resistance in NSCLC patients with and without EGFR mutations.
* To study the toxicity of erlotinib or gefitinib by correlating clinical toxicity with serum protein profile.
Significance:
An extensive profiling of the molecular circuitry affected by EGFR TKIs would be helpful in understanding the response and side effects of patients with NSCLC treated with erlotinib or gefitinib and could guide therapy and thus improve patient outcome.
