Mechanistic patient-specific predictive correlation of tumor drug response with microenvironment and perfusion measurements.

ABSTRACT: Physical properties of the microenvironment influence penetration of drugs into tumors. Here, we develop a mathematical model to predict the outcome of chemotherapy based on the physical laws of diffusion. The most important parameters in the model are the volume fraction occupied by tumor blood vessels and their average diameter. Drug delivery to cells, and kill thereof, are mediated by these microenvironmental properties and affected by the diffusion penetration distance after extravasation. To calculate parameter values we fit the model to histopathology measurements of the fraction of tumor killed after chemotherapy in human patients with colorectal cancer metastatic to liver (coefficient of determination R(2) = 0.94). To validate the model in a different tumor type, we input patient-s

SUBMITTER: Pascal J 

PROVIDER: S-EPMC3761643 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature