Altered cellular metabolism is a hallmark of cancer cells (Hanahan and Weinberg) and cells adapt their metabolism to fulfil the tumors needs for energy and building blocks for new cell structures. Almost a century after Otto Warburg’s observation that the glucose metabolism is altered in tumor cells, it is quite clear that these metabolic alterations are indeed important for tumor development and progression. However, the altered glucose metabolism is only one piece of the tumor metabolome puzzle. Amino acid metabolism, lipid metabolism and adenosine metabolism are also adapted and individual cancers appear to have distinct metabolic dependencies to sustain growth and proliferation. Furthermore, there is increasing evidence for a direct linkage between an altered tumor metabolism and tumor cell transformation, as the overexpression of oncogenes or the loss of tumor suppressor genes are key regulators of the accelerated glycolysis and glutaminolysis in tumors.
Tumor-driven shifts in metabolite abundance also lead to local immunosuppression and may thereby facilitate tumor progression and metastasis. We hypothesize, that oncometabolic changes represent possible target structures for cancer therapy. Targeting tumor cell metabolism is not only an approach to kill the tumor cell directly but also to overcome some limits of immunotherapy. Therefore, a systematic analysis of tumor and immune cell metabolism is required. Key technologies are well established in the laboratories of our consortium and we combine expertise in systems biology with expertise in cellular and clinical immunology for addressing these questions.