BREATHE Cohort: Single-center prospective cohort study, associated with a biocollection, from patients with metastatic bronchopulmonary carcinoma
Context:
Lung cancer is the 3rd most frequent tumor pathology in France with approximately 45,000 new cases diagnosed each year. The emergence of immunotherapy in recent years has transformed the prognosis of lung cancer, although it remains the leading cause of cancer mortality. Lung cancers are characterized by a great molecular heterogeneity that impacts the response to treatments.
Objectives:
The objective of this project is to build a bank of tumor samples (tumor samples, pleural fluid and blood samples) from patients with bronchial carcinoma. The diversity of the collected material should allow the construction of original in vitro culture models in 3 dimensions (explants and multicellular tumor spheroids). They will facilitate, in a life-like system, the analysis of the impact of anti-cancer therapeutics on tumor cells and the microenvironment from bronchial cancer surgical samples and pleural fluids. The variability of inter-individual responses can thus be studied with a better understanding of the mechanisms of therapeutic escape.
The second objective of this project is to prospectively collect blood samples from patients during the initiation of specific chemotherapy and/or immunotherapy treatments. Samples will be collected before treatment, during treatment and at relapse. From these samples, extracellular vesicles will be extracted in order to identify new predictive biomarkers of response or resistance to treatments.
The objective of the research project supported by the biocollection is to analyze the impact of standard chemotherapy treatments (platinum salts, gemcitabine, pemetrexed, paclitaxel -anti-PD(L)1)) on tumor cells and cells of the microenvironment of bronchial cancers. Our objective is to identify mechanisms of resistance to usual therapies, in order to propose new therapeutic strategies. Thanks to these tumor samples, various innovative in vitro cellular models will be developed, including flow culture of explants and multi-cellular tumor spheroids (MCTS) models. MCTS are 3-dimensional co-cultures of tumor cells (cell lines from the biocollection) with cells from the microenvironment (fibroblasts, macrophages, lymphocytes, endothelial cells, …) which reproduce some of the constraints of tumors (3-dimensional cell interactions, immunosuppression, diffusion constraints of therapeutic compounds and immune cells, …).
Study population
All tumor samples will be from patients with bronchial cancer, localized for operated tumors, locally advanced or metastatic for pleural fluids and blood samples. The tumor samples will come from surgical parts of operated patients. Pleural fluid samples (on average 100-500 ml) will be collected during pleural punctures performed as part of routine care. Blood samples (20 ml) will be collected from patients undergoing 1st line systemic treatment with chemotherapy and/or immunotherapy. Patients for whom operative tissue or pleural fluid will be available will also have blood samples taken to match the samples. The cell lines established from the collected samples (tumors and pleural fluids) will be sequenced to study the mutational status.
