Abstract
Tumour growth critically depends on a supportive microenvironment, including the tumour vasculature. Tumour blood vessels are structurally abnormal and functionally anergic which limits drug access and immune responses in solid cancers. Thus, tumour vasculature has been considered an attractive therapeutic target for decades. However, with time, anti-angiogenic therapy has evolved from destruction to structural and functional rehabilitation as understanding of tumour vascular biology became more refined. Vessel remodelling or normalisation strategies which alleviate hypoxia are now coming of age having been shown to have profound effects on the tumour microenvironment. This includes improved tumour perfusion, release from immune suppression and lower metastasis rates. Nevertheless, clinical translation has been slow due to challenges such as the transient nature of current normalisation strategies, limited in vivo monitoring and the heterogeneity of primary and/or metastatic tumour environments, calling for more tailored approaches to vascular remodelling. Despite these setbacks, harnessing vascular plasticity provides unique opportunities for anti-cancer combination therapies in particular anti-angiogenic immunotherapy which are yet to reach their full potential.