The study of liquid biopsy, together with the application of new targeted therapies, has revolutionized the oncology field. However more research is required to effectively apply these techniques into the clinical routine. Although lung cancer is currently one of the tumours in which molecular oncology has more impact, this tumour remains the leading cause of cancer related deaths worldwide, being the development of tools to guide the therapy selection and monitoring key points to improve this tumour survival rates. With the present thesis we investigated the value of different blood biomarkers for improving the management of advanced lung cancer patients through the analysis of circulating free DNA (cfDNA), circulating tumour cells (CTCs), and circulating proteins. We established and validated new protocols to characterize clinically relevant alterations in CTCs and ctDNA and demonstrated the potential of cfDNA monitoring as a prognostic and predictive tool in the context of both NSCLC and SCLC. Of note, we also identified a proteomic signature with value to predict immunotherapy response in patients with NSCLC. Overall, our results improve the knowledge and applicability of liquid biopsy analyses in patients with advanced lung cancer and help to advance in precision medicine
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