Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor.

Circulating biomarkers are of significant interest for cancer detection and treatment personalization. However, the biophysical processes that determine how proteins are shed from cancer cells or their microenvironment, diffuse through tissue, enter blood vasculature, and persist in circulation remain poorly understood. Since approaches primarily focused on experimental evaluation are incapable of measuring the shedding and persistence for every possible marker candidate, we propose an interdisciplinary computational/experimental approach that includes computational modeling of tumor tissue heterogeneity. The model implements protein production, transport, and shedding based on tumor vascularization, cell proliferation, hypoxia, and necrosis, thus quantitatively relating the tumor and circulating proteomes. The results highlight the dynamics of shedding as a function of protein diffusivity and production. Linking the simulated tumor parameters to clinical tumor and vascularization measurements could potentially enable this approach to reveal the tumor-specific conditions based on the protein detected in circulation and thus help to more accurately manage cancer diagnosis and treatment.