Non-Small Cell Lung Cancers (NSCLC) prognosis is still bad when tumors are not localized; any improvement will be based on earlier diagnosis and generation of new drugs. Both diagnosis and selection of the patients, who will respond to targeted therapies, require a precise definition of biomarkers.

The aim of the study is to identify secreted or targeted proteins from NSCLC and to validate their interest as seric biomarkers for diagnosis or prediction of response to therapy on a bank of more than 1000 annotated tumors and fluids collected during clinical protocols. We combine two methods to find new biomarkers: (i)identification of new "Cancer Testis" (CT) factors that are chromatin associated proteins based on the detection of antibodies directed against those factors in the sera of NSCLC patients or the detection of abnormal expression of testis-specific genes in lung tumor samples and (ii) Determination of secreted proteins by tumor cells (Secretome) and their comparison with normal epithelial lung cell lines followed by their identification in tissues and sera from NSCLC. In this context, we have shown that 2 growth factors, Insulin-like Growth Factor 1 (IGF1) and amphiregulin (AR), activate an original anti apoptotic pathway and we will validate the role of AR and/or IGF1 in resistance to treatment on clinical specimens (tumors and sera) from patients treated with Gefitinib. These tests on tumor and sera will be extended to the other discovered proteins.