Abstract
Inflammatory breast cancer (IBC) is a rare yet aggressive subtype of breast cancer, with a high mortality amongst others due to the lack of a specific treatment. The primary goal of this project is to strive towards a more comprehensive characterization of the tissue architecture and molecular complexity in IBC. This goal translates in two work packages. Firstly, we aim to investigate the communication between monocytes and B-lymphocytes, two cell types that are relevant to IBC biology based on available literature and our preliminary data. Secondly, using state-of-the-art technologies, we will Investigate the global composition of the tumor microenvironment in IBC beyond the cell types mentioned in the first aim. Then, the acquired knowledge of the composition of the tumor micro-environment and the molecular pathways of intercellular communication in IBC will be used to develop new strategies for targeted therapy. For this purpose, the use of preclinical models that optimally recapitulate tumor biology is quintessential. Therefore, this project will secondarily focus on the development of patient-derived tumor organoids (PDOs) that represent a significant advance for testing new treatment modalities. For this goal, again two work packages can be discerned. First, we aim to establish IBC PDOs that recapitulate the tissue architecture and molecular traits of primary IBC tissue samples as closely as possible. Secondly, we will use these organoid lines to test the efficacy of selected drugs in inducing cancer cell death and identifying predictive biomarkers of treatment response.
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