Physical modeling of drug transport in cancer

Abstract

Understanding the interaction of tumors with their microenvironment is imper ative to understand its development and to increase the efficiency of therapies. In addition to all other genetic and biochemical determinants of tumor system that make it very different than healthy tissue, morphological properties of tumor system and resulting physical properties add to this difference creating strong contrasts compared to its healthy counterpart. Therefore, examining the physics of this system is an im portant part of cancer research. In this work, we delve into the physics of tumor and its blood vessels to understand its role in tumor growth and response to therapy. We tried to resolve the physical problem of transport of drugs to tumor microenvironment efficiently. To achieve that, we created a tumor simulator by building a mathematical model framework that includes spatial representations of tumors and their microen vironment. Since vessels are the distributors of drugs and they are responsible for abnormal fluid flow, and resultant changes in fluid pressure, treatments manipulat ing tumors vessels were explored to enhance drug delivery. Specific models are built for simulating normalization of tumor blood vessels and promoting vessel growth with different treatments. These two approaches are tried using different doses of drug combinations and drug scheduling to optimize the benefit from chemotherapy. For each case, we revealed the advantages and disadvantages of these approaches and the physical reasons behind them.