Abnormal vasculature reduces overlap between drugs and oxygen in a tumour computational model: Implications for therapeutic efficacy

Abstract

The tumour microvasculature is abnormal, and as a consequence oxygen and drug transport to the tumour tissue is impaired. The abnormal microvasculature contributes to tumour tissue hypoxia, as well as to varying drug penetration depth in the tumour. Many anti-cancer treatments require the presence of oxygen to be fully efficacious, however the question of how well oxygen concentration overlaps with drug concentration is not elucidated, which could compromise the therapeutic effect of these drugs. In this work we use a computational model of blood flow and oxygen transport, and develop a model for an oxygen-dependent drug, T-DM1, to study the overlap of oxygen and drug concentration in tumour tissue, where we model both compressed and uncompressed vessels in the tumour. Our results show that, due to the compressed vessels present in tumours, areas of sufficient oxygen concentration for a drug to function overlap poorly with areas of sufficient drug concentration, covering 28% of the tumour tissue, compared to 82% in healthy tissue. The reduction in drug and oxygen overlap is due to the altered red blood cell dynamics through the abnormal microvasculature, and indicates that drug transport to tumours should not be considered independently of oxygen transport in cases where the drug requires oxygen to function.