Abstract
Heterogeneity in oxygen distribution in solid tumours is recognised as a limiting factor for therapeutic efficacy. Vessel normalisation strategies, aimed at rescuing abnormal tumour vascular phenotypes and alleviating hypoxia, have become an established therapeutic strategy. However, understanding of how pathological blood vessel networks and oxygen transport are related remains limited. In this paper, we establish a causal relationship between the abnormal vasculature of tumours and their heterogeneous tissue oxygenation. We obtain average vessel lengths 
and diameters 
from tumour allografts of three cancer cell lines and observe a substantial reduction in the ratio 
compared to physiological conditions. Mathematical modelling reveals that small values of the measured ratio λ (i.e. λ < 6) can bias haematocrit distribution in tumour vascular networks and drive highly heterogeneous tumour tissue oxygenation. Finally, we show an increase in the average λ value of tumour vascular networks following treatment with the DC101 anti-angiogenic cancer agent. Based on our findings, we propose a new oxygen normalisation mechanism associated with an increase in λ following treatment with antiangiogenic drugs.
