Consortium at a Glance
The Work Package 1 (WP1)
“Linking Dynamic Properties of the Erythropoietin Receptor on Lung Cancer Cells”.
The aim is to detect the presence of a functional EpoR (Erythropoietin Receptor) in lung cancer cells and the role in the signaling for tumor progression. Critical parameters determining and distinguishing EpoR activation and signaling initiation in normal and tumor cells will be identified. In addition the connection between the activation of EpoR in tumor and normal cells with the gene/microRNA netwoks will be determined. Finally live cell imaging studies will be performed to describe reaction-diffusion models and identify critical differences in the tumor signal activation. These critical differences will be determinant to design new therapeutic strategies.
The Work Package 2 (WP2)
“Modeling of Epo Effects on Tumor-Stroma Interaction: Promotion of Angiogenesis and Synergy of Epo and VEGF”.
The aim is to establish in vitro models of tumor-stroma interaction and a tissue-wide approach to analyse, model and predict cell fate decisions ruled by Epo induced gene network dynamics. These studies will facilitate the development of a mechanistic mathematical and link this to an integrative multi-scale model of vessel sprouting that will mimic pattern formation on the multi-cellular level. This will allow to predict the effect of Epo on the multi-cellular phenotype in vitro and providing links to effects in animal model and in humans.
The Work Package 3 (WP3)
“Multi-scale Modeling of Tumor-Promoting Epo Effects: Development of Surrogate Markers and Small Animal Imaging”.
The aims is to develop a data based mathematical model that integrates the interaction of the tumor tissue in vivo and its interference with the chemotherapy. This mathematical model will be useful to predict the tumor behavior in vivo. Data will encompass dynamic imaging of tumor perfusion, VEGFR2 expression (molecular ultrasound imaging) and EpoR expression after development of a near infrared optical probe and a PET probe that will be possible used as a clinical tracer at the end of the project. This will be complemented by optimizing pharmacokinetic models for post processing of DCE MRI and DCE CT data and by the development of a user friendly software. This software will be extremely helpful to our clinical partners to analyze data of patients.
The Work Package 4 (WP4)
“Risk-Benefit Prediction for the Clinical Use of Epo Imaging of Patients”.
The aim is to validate the mathematical models on the effect of Epo on tumor malignancy that were established in experimental lung cancer cell models (WP1, WP2, WP3) for patients tumors. To this end SOPs will be optimized/modified for isolation, characterization and establishment of primary fibroblasts, epithelial tumor cells/cell lines from NSCLC patient tissue. Patients treated by chemotherapy with/without Epo will be monitored for tumor progression. The specific EpoR-recognizing probes (developed in WP3) will be tested in patients. The adapted multi-scale models will allow clinicians to predict Epo effects for individualized patient therapy.