Volume 45 Issue 6, June 2024

Cover Credit: In this cover article, Zhou et al. constructed a novel mechanistic quantitative systems pharmacology model describing the underlying pathophysiological processes of HER2+BC, from ligand-receptor binding to downstream signaling and finally to tumor growth, while incorporating the distinct modalities and mechanisms of various state-of-the-art therapeutics. A large variety of in vitro and in vivo experimental data was used during model calibration and validation, achieving a quantitative and accurate description of cellular signaling, time-response, dose-response, and tumor growth kinetics. In a high-throughput manner, this multiscale QSP model platform enabled researchers to probe into the efficacy of different therapeutic strategies at the preclinical level, generate new hypothesis regarding best treatment combinations to overcome resistance, and suggested important directions for future translational drug research and model-informed drug development. Doi:10.1038/s41401-024-01232-9. See the article in pages 1287–1304