Thermodynamic Genome-Scale Metabolic Modeling of Metallodrug Resistance in Colorectal Cancer

Background: Mass spectrometry-based metabolomics approaches provide an immense opportunity to enhance our understanding of the mechanisms that underpin cellular reprogramming cancers. Accurate comparative metabolic profiling heterogeneous conditions, however, is still a challenge. Methods: Measuring both intracellular and extracellular metabolite concentrations, we constrain four instances thermodynamic genome-scale model HCT116 colorectal carcinoma cell line compare flux profiles cells are either sensitive or resistant ruthenium- platinum-based treatments with BOLD-100/KP1339 oxaliplatin, respectively. Results: Normalizing according growth rate normalizing their respective controls, able dissect responses specific drug resistance states. We find normalization steps be crucial in interpretation data show limited select number pathways. Conclusions: Here, elucidate key importance data, allowing us uncover drug-specific during acquired metal-drug resistance.