J. Betge and J. Schott hypothesise that specific microbial metabolites affect translation control and thereby plasticity and drug resistance in CRC, mediated by mTOR-dependent and -independent mechanisms. In P7 J. Betge and J. Schott will analyse the activity and heterogeneity of central regulators of translation in PDOs and mouse tumours upon treatment with standard-of-care drugs and investigate the effect of microbial metabolites on translation control under therapeutic pressure. Using RNASeq, RiboSeq and proteomics, they will gain a detailed view on mechanisms of drug tolerance/resistance, which integrates the layer of translation efficiency. Finally, they will connect their findings with the analysis of clinical samples from CRC patients. This may lead to the identification of mechanisms and targets to overcome adaptive treatment resistance.