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While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization.
Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression.
In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials.
The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drugβdrug, or drugβmetabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach. Keywords: systems biology, PBPK, software, multiscale, modeling, simulation, oncology, signal transduction. Most properties of a biological organism result from complex interactions between biological scales from the molecular level to the whole body.
