Cells, tissues, and organs on chips: challenges and opportunities for the cancer tumor microenvironment

The transition to increasingly sophisticated microfluidic systems has led to the emergence of "organ-on-chip" technology that can faithfully recapitulate organ-level function. Given the rapid progress at the interface between microfluidics and cell biology, there is need to provide a focused evaluation of the state-of-the-art in microfluidic systems for cancer research to advance development, accelerate discovery of novel insights, and facilitate cooperation between engineers, biologists and oncologists in the clinic. Here, we provide a focused review of microfluidics technology from cells- and tissues- to organs-on-chips with application toward studying the tumor microenvironment. Key aspects of the tumor microenvironment including angiogenesis, hypoxia, biochemical gradients, tumor-stromal interactions, and the extracellular matrix are summarized for both solid tumors and non-solid hematologic malignancies. An overview of microfluidic systems designed specifically to answer questions related to different aspects of the tumor microenvironment is provided, followed by an examination of how these systems offer new opportunities to study outstanding challenges related to the major cancer hallmarks. Challenges also remain for microfluidics engineers, but it is hoped that cooperation between engineers and biologists at the intersection of their respective fields will lead to significant impact on the utility of organs-on-chips in cancer research.