Lung cancer is currently the most common malignancy and the leading cause of cancer-related death worldwide, varying significantly among geographical areas, sex of patients and distinct populations. Since 1970, incidence, and specific histological characteristics of lung cancer have been significantly modified; however, a disappointing survival rate still persists. A potential steroid relation of lung cancer might be of interest, in view of hormone replacement therapies and contraception strategies followed by a wide part of female population. Hence, the lung remains a favorite site for distant metastases of prostate and breast carcinomas and within this context, a well-established steroid receptor profiling could be crucial in differential diagnosis of primary lung tumors from metastatic foci. Aim of this study is the investigation of the function and the role of sex steroid receptors (both nuclear and extranuclear) in Non-Small Cell Lung Carcinomas (NSCLCs) and their possible prognostic, diagnostic and therapeutic relevance, in association with survival and therapeutic response of patients. Our approach includes three distinct but interrelated objectives: (1) Detection and action of ER and AR in NSCLC cell lines. In this objective, basic research on cells will be initiated. Different ER and AR (intracellular, nuclear and membrane-associated) receptors will be assayed by different methodologies, providing a receptor spectrum of each cell line and providing the more appropriate tools for the detection of the same parameters in human specimens; (2) performing pre-clinical pharmacology studies of SR implication in animal models; (3) validating our findings in clinical specimens and their relation with other established biomarkers, in view of their implementation as potential diagnostic, prognostic or tailored therapeutic targets.
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