Systems Biology of Tumor Microenvironment

Louis T. Curtis, Hermann B. Frieboes

Katarzyna A. Rejniak

Although extensive research effort and resources have been dedicated to the development of nanotherapeutics to treat cancer, few formulations have reached clinical application. A major reason is that the large number of parameters available to tune nanotherapy characteristics coupled with the variability in tumor tissue precludes evaluation of complex interactions through experimentation alone. In order to optimize the nanotechnology design and gain further insight into these phenomena, mathematical modeling and computational simulation have been applied to complement empirical work. In this chapter, we discuss modeling work related to nanotherapy and the tumor microenvironment. We first summarize the biology underlying the dysregulated tumor microenvironment, followed by a description of major nano-scale parameters. We then present an overview of the mathematical modeling of cancer nanotherapy, including evaluation of nanotherapy in multi-dimensional tumor tissue, coupling of nanotherapy with vascular flow, modeling of nanotherapy in combination with in vivo imaging, modeling of nanoparticle transport based on in vitro data, modeling of vasculature-bound nanoparticles, evaluation of nanotherapy using pharmacokinetic modeling, and modeling of nano-based hyperthermia. We conclude that an even tighter interdisciplinary effort between biological, material, and physical scientists is needed in order to eventually overcome the tumor microenvironment barrier to successful nanotherapy.