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

## TL;DR

Abnormal blood vessels in tumors reduce the overlap of oxygen and drugs, which may lower the effectiveness of oxygen-dependent cancer treatments.

## Contribution

A computational model reveals how abnormal tumor vasculature reduces the overlap of oxygen and drug concentrations, impacting therapeutic efficacy.

## Key findings

- Compressed vessels in tumors lead to poor overlap between oxygen and drug concentrations in 28% of tumor tissue.
- Healthy tissue shows 82% overlap of oxygen and drug concentrations compared to tumor tissue.
- Altered red blood cell dynamics in abnormal vasculature reduce drug and oxygen overlap.

## 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.

In tumours, abnormal vascular structures compromise blood flow and, as a consequence, tumour tissue is hypoxic and drug delivery is poor. In addition, some drugs require the presence of oxygen for maximum therapeutic efficacy. While oxygen and drugs are both delivered to the tissue by the blood vessels, they are transported via different mechanisms. This work investigates, through mathematical modelling of blood flow and drug transport in a model microvascular network, how the overlap of oxygen and drugs is impaired by abnormal vascular structures in tumours. The findings show that, when vessels are compressed by tumour tissue, the different modes of transport of oxygen and drugs lead to a reduced overlap of drugs and oxygen in the tumour tissue, compromising the therapeutic efficacy of the oxygen-dependant modelled drug. Therefore, for oxygen-dependent drugs, optimising for this overlap should guide the design of future therapeutic strategies.