SUMMARYWe investigate the impact of the tumor microvascular geometry on transport of drugs in solid tumors, in particular focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations which is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells. The coefficients are then injected into the macroscale equations, which are solved for an isolated, vascularized spherical tumor. We consider the effect of vascular tortuosity on the transport of anti-cancer molecules, focusing on the Vinblastine and Doxorubicin dynamics, which can be considered a tracer and a highly interacting molecule, respectively. The computational model is able to quantify the performance of the treatment through the analysis of the interstitial drug concentration and the quantity of drug metabolized in the tumor. Our results show that both drug advection and diffusion are dramatically impaired by increasing geometrical complexity of the microvasculature, leading to non-optimal absorption and delivery of therapeutic agents. However, this effect apparently has a minor role whenever the dynamics are mostly driven by metabolic reactions in the tumor interstitium, i.e. for highly interacting molecules. In the latter case, anti-cancer therapies that aim at regularizing the microvasculature might not play a major role and different strategies are to be developed.