TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model

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Liver cancer (LC) represents the sixth most frequent cancer disease and third most frequent cancer related cause of death with rising incidence even in industrialized countries. It comprises Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, and primary liver tumors of mixed differentiation. LC represents an ideal model for solid cancer: major, well documented cancer risk factors are relevant for LC, namely chronic viral infection (Hepatitis B/C), obesity/metabolic syndrome (Non-alcoholic steatohepatitis), toxic injury (alcohol/aflatoxin) and chronic inflammation; still, little is known in regard to the oncogenic mechanism by which the established risk factors drive LC development, how lethal tumor progression takes place in its specific microenvironment, and how to improve treatment approaches accordingly. With excellent model systems available in LC, especially innovative mouse technologies and well annotated human LC cohorts, which reflect its causes and molecular changes, we can solve these questions.The SFB/TR 209 integrates and exploits this strong and exemplary model system constellation and the expertise of internationally leading LC researchers to tackle the relevant mechanistic and interventional questions in a coordinated and complementary manner. Research area A concentrates on tumorigenic mechanisms of the increasingly leading LC etiology in the Western World, Non-alcoholic steatohepatitis, and the main effector mechanism, chronic inflammation. Research area B investigates key progression mechanisms that shape the interaction between the LC cell and its environment, such as complex regulatory tumor cell mechanisms, tumor cell plasticity, and tumor-stroma interaction. Research area C concentrates on novel, bedside-bench-driven therapeutic approaches mainly addressing the stroma compartment, i. e. tumor immune response and vasculature. Model systems evaluation, biobanking, data storage and bioinformatics analyses issues are concentrated in the central INF-project providing a harmonized and sustainable approach to models, biological samples and data. The research efforts of the SFB/TR 209 are well linked to strong LC translational and clinical structures at all three partner sites. Existing efficient structures addressing the promotion of junior scientists, the compatibility of family and career, and gender issues established at all three partner sites will be used and specifically complemented by the SFB/TR 209. Built on its strong research track, complementary and cooperative research program, and linked to well established translational structures, the SFB/TR 209 gains relevant new mechanistic insights and interventional strategies that are expected to impact on other solid tumor diseases even beyond this clinically relevant model cancer.