Comparison of drug inhibitory effects (IC50) in monolayer and spheroid cultures

Traditionally, the monolayer (two-dimensional) cell cultures are used for initial evaluation of the ef-fectiveness of anticancer drugs. In particular, these experiments provide the IC 50 curves that determine drug concentration that can inhibit growth of a tumor colony by half when compared to the cells grown with no exposure to the drug. Low IC 50 value means that the drug is effective at low concentrations, and thus will show lower systemic toxicity when administered to the patient. However, in these experiments cells are grown in a monolayer, all well exposed to the drug, while in vivo tumors expand as three-dimensional multicellular masses, where inner cells have a limited access to the drug. Therefore, we performed computational studies to compare the IC 50 curves for cells grown as a two-dimensional monolayer and a cross section through a three-dimensional spheroid. Our results identified conditions (drug diffusivity, drug action mechanisms and cell proliferation capabilities) under which these IC 50 curves differ significantly. This will help experimentalists to better determine drug dosage for future in vivo experiments and clinical trials.