Human Microcirculation-on-Chip Models in Cancer Research: Key Integration of Lymphatic and Blood Vasculatures

Cancer metastasis is a highly complex and multistep process, which is initiated by the invasion of tumor cells into the microcirculation system. A diverse variety of organ-on-chip models are described investigating this critical event. However, most of these models solely integrate the blood vasculature and overlook the fundamental role of the lymphatic system despite the solid evidence showing that cancer cells mainly use this vascular network to initiate metastasis. Herein, the latest advances in the field of organ-on-chip models of the human microcirculation system in cancer research are reviewed. The reported models are employed to investigate the mechanistic determinants of tumor physiopathology and for the screening of new anticancer drugs under the scope of the microcirculation bed. Overall, the development of complete microcirculation-on-chip models integrating the blood and lymphatic vasculatures is expected to provide key insights into the drug delivery process, the screening of novel therapeutic compounds, or the mechanism of tumor invasion and metastasis, among others.