On-chip modeling of tumor evolution: Advances, challenges and opportunities

Tumor evolution is the accumulation of various tumor cell behaviors from tumorigenesis to tumor metastasis and is regulated by the tumor microenvironment (TME). However, the mechanism of solid tumor progression has not been completely elucidated, and thus, the development of tumor therapy is still limited. Recently, Tumor chips constructed by culturing tumor cells and stromal cells on microfluidic chips have demonstrated great potential in modeling solid tumors and visualizing tumor cell behaviors to exploit tumor progression. Herein, we review the methods of developing engineered solid tumors on microfluidic chips in terms of tumor types, cell resources and patterns, the extracellular matrix and the components of the TME, and summarize the recent advances of microfluidic chips in demonstrating tumor cell behaviors, including proliferation, epithelial-to-mesenchymal transition, migration, intravasation, extravasation and immune escape of tumor cells. We also outline the combination of tumor organoids and microfluidic chips to elaborate tumor organoid-on-a-chip platforms, as well as the practical limitations that must be overcome.