“Systems Biology” – A novel approach to The Lung Cancer Problem

Lung cancer is one of the most fatal cancers world-wide with 1.3 million deaths per year and this number is still rising. Around 80% of the lung cancer cases are identified as Non-Small Cell Lung Cancer (NSCLC). One of the main reasons for the deadly outcome is the early metastatic spread observed in the majority of patients. Many patients are diagnosed at rather late stage of the disease and so that tumor cells have already spread out into other region of the body. In this situation therapeutic options are systemic chemotherapy or, if specific alterations are uncovered, targeted therapy with tyrosine kinase inhibitors. Unfortunately, the success of these therapies is usually only transient and therapy resistance develops. Tumor development and therapy resistance are complex processes that are determined through intertwined interactions across different levels. To disentangle this complexity and address dynamic properties, a Systems Biology approach is required that combines extensive generation of quantitative data with different mathematical concepts. This will help to gain insights into mechanisms that promote early metastatic spread and will facilitate the development of improved diagnosis and treatment, and thus enable us to address topics of uttermost clinical relevance.

Preventing the Risk of Epo Treatment

As a side effect of chemotherapy patients frequently develop anemia. For the treatment of anemia recombinant erythropoietin (Epo) can be applied that stimulates the production of red blood cells. However, Epo receptors (EpoR) have been observed both in tumor cell lines, and lung tumors and a clinical trial showed a shortened progression-free survival in the patients treated with Epo. The aim of the BMBF-funded LungSys I consortium in the MedSys call was to identify the effects of EPO treatment in lung cancer from the protein to the organ level, integrating experimental data into a multi-scale model and designing strategies to avoid anemia.

Molecular processes of early tumor spread and drug resistance in Lung Cancer

Early metastatic spread involves multiple serial steps such as separation from the primary tumor mass, invasion of the surrounding tissues, entry into the blood stream and invasion of other organs. There is an increasing list of somatic mutations in lung carcinoma. Among those are activating mutations of the epidermal growth factor receptor (EGFR) for some of which can be treated by targeted therapy. However, therapy resistance rapidly arises. Factors such as hepatocyte growth factor (HGF), transforming growth factor beta (TGFbeta), insulin-like growth factor 1 (IGF-1R) and erythropoietin receptor (EpoR) are thought to contribute to therapy resistance. The aim of the BMBF-funded LungSys II consortium in the CancerSys call is to apply a Systems Biology approach to identify parameters that critically determine early spread and to predict possibilities for improved therapeutic options.