Organ on Chip Technology to Model Cancer Growth and Metastasis

Abstract

Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell–cell and cell–matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented.

Capturing the spatial and temporal dynamics of tumor stroma for on-chip optimization of microenvironmental targeting nanomedicine

“…The TME is the complex and dynamic context in which tumor formation and growth occur; it presents specific physical and biochemical features involved in regulating neoplastic cell differentiation, proliferation, invasion, and metastasis. 20 The TME consists of tumor cells, tumor stromal cells including stromal fibroblasts, endothelial cells and immune cells and the non-cellular components of the ECM composed of several macromolecules including collagen, proteoglycans ( i.e. heparan sulfate, versican and hyaluronan) and glycoproteins ( i.e.…”

“…Consequently, tumor/microenvironment crosstalk in pathogenesis and drug screening can be replicated on-chip by reproducing the interaction of neoplastic cells with endothelial, fibroblast and immunity cells, all populating the ECM. 20 Furthermore, these miniaturized systems offer the chance to high-throughput screen a plethora of molecules and substances, reducing costs and ethical issues and enhancing reproducibility. Tumor-on-chip platforms can be used for evaluating novel nanomedical approaches based on target therapy with the aim to minimize drug toxicity, increase specificity and speed up clinical translation.…”

Three-Dimensional in Vitro Models: A Promising Tool To Scale-Up Breast Cancer Research

“…Concerning the tumor-on-chip platforms, they were created to mimic controlled culture conditions with the goal of studying blood circulation, medication administration, and intravasation and extravasation mechanisms that occur during tumor formation. Unfortunately, some of the limitations of adopting such platforms include the intensive user training necessary for multistep manufacturing, unique equipment, small-volume culture, and problems in saving seeded cells for other characterization …”

“…Unfortunately, some of the limitations of adopting such platforms include the intensive user training necessary for multistep manufacturing, unique equipment, small-volume culture, and problems in saving seeded cells for other characterization. 178 Furthermore, 3D microenvironments, unlike in vivo animal models, lack vasculature as food supply and transportation of normal small molecules. These models reproduce static or short-term environments and will not predict cross-talk with other cells or their impact on the culture.…”

Evolution of Models of Prostate Cancer: Their Contribution to Current Therapies

“…Organ-on-chip model arose as a great technological advance, reforming biomedical research and drug discovery, by mimicking the structure and functionality of organs in vitro. Regarding oncology research, organ-on-a-chip is able to replicate key aspects of the tumor microenvironment, like biochemical gradients and niche factors, cell-cell and cellmatrix interactions, and complex tissue structures composed of tumor and stromal cells (20).…”