3D Modeling of Epithelial Tumors—The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology

Abstract

The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This review focuses on the origin and mechanism of epithelial cancers, followed by experimental models designed to recapitulate the epithelial cancer structure and microenvironment, such as 2D and 3D cell culture models and animal models. A specific focus is put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models utilizing biomaterials of natural or synthetic origins. Further emphasis is laid on high-content imaging technologies that are used in the field to visualize in vitro models and their morphology. The associated technological advancements and challenges are also discussed. Finally, the review gives an insight into the potential of exploiting nanotechnological approaches in epithelial cancer research both as tools in tumor modeling and how they can be utilized for the development of nanotherapeutics.

3D Tumor Models in Urology

“…Recent developments are in bioprinting of epithelial tumor models, for which natural as well as synthetic ECM components and different cell types can be used. This allows replication of a structured tissue with vascularization [ 112 ].…”

Lung cancer organoids: models for preclinical research and precision medicine

“…3. Organoids require integration with advanced biotechnologies to optimize their functionality ( 130 ). By combining organoids with single-cell technology, it is possible to determine whether tumor organoids can accurately represent the heterogeneity of lung cancer and gain insight into lung cancer development through organoid models ( 16 , 45 ).…”

Lung Cancer Organoids: The Rough Path to Personalized Medicine

“…Lung cancer cell lines have been used to produce tumor spheroids, which have been used for multiple studies including analyses of molecular crosstalk in a tumor microenvironment (TME), identification of cell–to-cell interactions, and drug screening [ 7 ]. Cell-line-based spheroids provide drug responses more similar to those of tumors in vivo as compared to 2D cultures, as their multi-layer structure with hypoxic, senescent, and necrotic areas can, to some degree, mimic the solid tumor architecture [ 8 ]. Moreover, the cheapness and reproducibility of cell-line-derived spheroids are advantageous for testing the physicochemical properties of drug candidates, such as drug penetration [ 7 ].…”

“…Furthermore, Matrigel composition (60% laminin, 30% collagen IV, 8% entactin, and 2–3% perlecan) [ 92 ] does not reflect the composition of the lung connective tissue, which is mainly based on collagen I and III fibers [ 93 ]. A variety of natural and synthetic materials are being explored as alternatives to Matrigel for organoid cultures [ 8 , 92 , 94 , 95 , 96 ]. Briefly, alternative scaffolds for organoid cultures can be divided in natural and synthetic substrates [ 92 ].…”