01730nas a2200253 4500000000100000000000100001008004100002260000900043653002100052653001900073653001500092653001800107653002700125100002100152700001500173700001800188700001800206245008300224856006700307300001200374490000700386520106900393022001401462 2024 d c202410acancer-on-a-chip10aDrug screening10ametastasis10amicrofluidics10aTumor Microenvironment1 aAnastasia Brooks1 aYali Zhang1 aJiezhong Chen1 aChun-Xia Zhao00aCancer Metastasis-on-a-Chip for Modeling Metastatic Cascade and Drug Screening uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202302436 a23024360 v133 aMicrofluidic chips are valuable tools for studying intricate cellular and cell–microenvironment interactions. Traditional in vitro cancer models lack accuracy in mimicking the complexities of in vivo tumor microenvironment. However, cancer-metastasis-on-a-chip (CMoC) models combine the advantages of 3D cultures and microfluidic technology, serving as powerful platforms for exploring cancer mechanisms and facilitating drug screening. These chips are able to compartmentalize the metastatic cascade, deepening the understanding of its underlying mechanisms. This article provides an overview of current CMoC models, focusing on distinctive models that simulate invasion, intravasation, circulation, extravasation, and colonization, and their applications in drug screening. Furthermore, challenges faced by CMoC and microfluidic technologies are discussed, while exploring promising future directions in cancer research. The ongoing development and integration of these models into cancer studies are expected to drive transformative advancements in the field. a2192-2659