Optimizing Vessel Normalization and Chemotherapies to Control Tumor Growth

Abstract

The search for efficient chemotherapy drugs would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we establish a multi‐scale mathematical model of the tumor microenvironment to simulate three‐dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to control tumor progression. The chemotherapy approaches include: single anti‐cancer or anti‐angiogenic drug, combined anti‐cancer and anti‐angiogenic drugs, metronomic (low dose‐high frequency) anti‐cancer drug, and metronomic‐combined anti‐cancer and anti‐angiogenic drugs. We show that metronomic chemotherapy with one day frequency produces responses very similar to the higher frequency, low dose, but should result in lower toxicity. We further simulate different sequences of treatments to optimize combination anti‐angiogenic and chemotherapies. The computational results of chemotherapy performance in response to anti‐cancer and anti‐angiogenic drugs are in good agreement with experimental measurements.