Figure 1.

Comparison between an EPR-sensitive tumor phenotype (typical of preclinical cancer models) and an EPR-insensitive tumor phenotype (typical of clinical human tumors). EPR-sensitive tumors are characterized by a hyperpermeable vasculature with large endothelial fenestrations, uniformly low pericyte coverage, a relatively sparse extracellular matrix, and a small immune profile. In contrast, the EPR-insensitive phenotype has a more well-developed and branched vasculature, smaller endothelial fenestrations, heterogeneously high or low pericyte coverage, a relatively dense extracellular matrix, and a more developed immune profile. These characteristics exist on a spectrum - EPR-based delivery strategies operate best on a subset of EPR-sensitive tumors, whereas EPR-adaptive delivery strategies are designed to function across this spectrum.