Investigation of cancer response to chemotherapy: a hybrid multi-scale mathematical and computational model of the tumor microenvironment.

Abstract

Tumor microenvironment (TME) is a multi-scale biological environment that can control tumor dynamics with many biomechanical and biochemical factors. Investigating the physiology of TME with a heterogeneous structure and abnormal functions not only can achieve a deeper understanding of tumor behavior but also can help develop more efficient anti-cancer strategies. In this work, we develop a hybrid multi-scale mathematical model of TME to simulate the progression of a three-dimensional tumor and elucidate its response to different chemotherapy approaches. The chemotherapy approaches include multiple low dose (MLD) of anti-cancer drug, maximum tolerated dose (MTD) of anti-cancer drug, combination therapy of MLD and anti-angiogenic drug, and combination therapy of MTD and anti-angiogenic drug. The results show that combining anti-angiogenic agent with anti-cancer drug increases the performance of cancer treatment and decreases side effects for normal tissue. Indeed, the vascular normalization caused by anti-angiogenic therapy improves anti-cancer drug delivery for both MLD and MTD approaches. The results show that anti-cancer drug administered in a lower dose than the maximum tolerated dose repetitively over a long period treats cancer with a considerable performance and fewer side effects. We also show that tumor morphology and distribution of cancer cell phenotypes can be considered asthe characteristics to distinguish different chemotherapy approaches. This robust model can be applied to predict the behavior of any type of cancer and quantify cancer response to different chemotherapy approaches. The computational results of cancer response to chemotherapy are in good agreement with experimental measurements.