Systems modelling of the EGFR-PYK2-c-Met interaction network predicts and prioritizes synergistic drug combinations for triple-negative breast cancer

摘要

Author summary We applied a systems modelling approach combining mechanistic modelling and biological experimentation to identify effective drug combinations for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with no approved targeted treatment. The model predicted and prioritized the synergistic combinations as confirmed by experimental data, demonstrating the power of this approach. Moreover, analysis of clinical data of TNBC patients and patient-specific modelling simulation enabled us to stratify the patients into subgroups with distinct susceptibility to specific drug combinations, and thus defined a subset of patient that could benefit from the combined treatments.