Tumor-on-a-chip models of the human microcirculatory system as a key tool for cancer metastasis research

Cancer is the second cause of death worldwide. Most of the cancer-related deaths are due to the metastasis, which involves a complex cascade of events[1] being tumour cell extravasation the rate limiting step.

A big effort is being done to unveil cancer mechanistic determinants. In vitro models fail to reproduce the complexity of the tumour microenvironment. In vivo animal models recapitulate the biological complexity of a living system but lack the immune system what affects cancer dissemination and the therapeutic response. As a result, there is a need to design novel in vitro assays capable of recapitulating tissue-tissue interfaces as well as the in vivo-like microenvironment. In this sense, tumour-on-a-chip (ToC) models emerges as a very attractive approach for studying cancer and metastasis processes since they allow reproducing one or several steps of the cancer metastasis cascade. Importantly, ToC models can mimic the hydrodynamic characteristics of the cancerous and normal microcirculatory system, formed by blood and lymphatic vessels. Tumour cells use the lymphatic system to promote metastasis to lymph nodes and distant organs. As a result, and due to the critical role of the lymphatic system in cancer metastasis, cancer models including both blood and lymphatic vessels are needed. Herein, we review the latest advances in the field of ToC models of the human microcirculatory system.