Analysing the regulation of metabolic transformation in breast cancer
Cells in a non-transformed matrix in an organ or the tissue can develop progressively to a neoplastic condition. The reprogramming of the energy metabolism thereby makes up an important milestone for the development of tumours. Otto Warburg was a pioneer in this field and discovered – as early as in the 1920s - that cancer cells, even when sufficiently supplied with oxygen, preferably metabolise glucose through glycolysis, a process that avoids the oxidative phosphorylation (OXPHOS). Aggressive cancer cells benefit from high glucose uptake rates allowing them to produce higher quantities of ATP, if cells reprogramme the glycolysis of OXPHOS to lactate production. Reduced OXPHOS, however, will lead to a less effective production of important metabolites. These compounds make up the basic building blocks of the synthesis of amino acids, nucleotides or lipids, though these will be exceptionally needed when it comes to an increased proliferation of tumour cells. Consequently, a support mechanism was detected in tumour cells that feeds the cancer cycle by means of taking up amino acids. Therefore, our work aims at developing a basic model that allows the identification of key mechanisms that might help to degrade malign signal processes that have led to an altered metabolism in cancer cells systematically. Consequently, the anabolic and exploiting metabolism of tumour cells should be returned to a metabolism of non-transformed cells. Thereby, the viability of tumour cells will be reduced which makes them susceptible to effective treatment. We work with constrained mathematic models that describe the equilibrium states of tumour metabolism and that are based upon existing experimental high-throughput data.