Challenge

For many human diseases, there is a strong unmet need to identify cells that in particular prefer an anaerobic over an aerobic environment (aerotolerant anaerobes). This ability of cell growth under anoxia (oxygen deficiency) is still unexploited in the understanding and the treatment of many diseases, where anaerobic cells in an anoxic micro-environment have a selective growth advantage over aerobic cells and thus are drivers of disease progression, e.g. in cancer.

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This method provides a functional qualitative assay that can detect cells that grow preferably under anoxia (aerotolerant anaerobes). It mimics the in vivo anoxic microenvironment that is an important driver for many human diseases giving rise to a population of cells that can grow very fast independent of the local oxygen supply. PK M2 is a typical marker of fast proliferating non-malignant and cancer cells. It redirects glucose carbons to nucleotide, protein and lipid synthesis reducing the doubling time of cancer cells under anoxia (1, 2). Being the bottle neck for glucose flux, PK M2 and LDH regulate anaerobic anabolism and anaerobic energy supply (2). Thus the activity of PK and LDH in the homogenates determines the presence of cells with the potential to grow fast under anoxia (aerotolerant anaerobes).