The research themes of the Meuwissen lab focus on understanding the biology of lung cancer. Studying the molecular and cellular biology of lung cancer should provide a better insight into its onset and progression, but also lead to new molecular mechanisms for lung tumor intervention. The latter findings can then be tested in preclinical mouse models followed by translation into new clinical therapies against lung cancer.
Although the biology of lung cancer is complex, its phenotypical characteristics are very specific and well defined. In the past decades, most molecular pathways and major genetic lesions that govern the onset and progression of lung cancer have been identified. In our previous work, we developed somatic mouse models that mimic both human Non-Small Cell Lung Cancer (NSCLC) as well as Small Cell Lung Cancer (SCLC). We characterized these models and made them ready for basic and applied translational research. Further analyses with our SCLC mouse models revealed a functional link between tumor cell heterogeneity and tumor progression in the form of metastasizing capacity. Active epithelial-mesenchymal transition (EMT) was shown to take place inside individual SCLC lesions and governs the extent of tumor heterogeneity. We follow up on these previous studies to investigate the molecular mechanisms of EMT in SCLC and its effect not only on tumor progression but also on acquired chemotherapy resistance. In our studies with an NSCLC model, we found that the complete loss of β1 integrin could block the onset and tumor progression of KRAS-driven lung cancer. This novel finding opens a way to study how β1 integrin-dependent intracellular signaling interacts with KRAS pathway and could possibly lead to new molecular targets for therapeutic intervention. Currently, we established the first series of human lung cancer PDX models and we are refining them on a humanized mouse background.
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