Incorporating Cellular Metabolism into Growth Models of Multicellular Tumor Spheroids

Many chemotherapeutic strategies have failed due to pronounced diffusion limitations in tumors induced by poor vasculaturization. Diffusion limitations, present in threedimensional tissue, produce nutrient deficient regions that eventually become necrotic in tumors in vivo. Multicellular spheroids are better models of in vivo tumors than monolayer cultures because they mimic the heterogeneous microenvironments present in tumors (Sutherland, 1988). Because the growth progression of spheroids in the presence of diffusion limitation is not fully understood, the development of predictive models for the growth of in vitro spheroids has received considerable attention. Such predictive models can be used to guide the design of better chemotherapeutic strategies.