3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness

Abstract

The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative “gold standard”, tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression.

On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening

“…As a result, there is growing interest in the development and use of 3D cancer in vitro models for the replacement of 2D in vitro models and reduction in the use of animal models, the latter of which is an important objective in terms of the 3R framework (replace, reduction, and refinement of animals) [ 41 , 42 ]. 3D models for pre-clinical treatment testing are emerging to more realistically recapitulate TMEs, and more specifically TME hallmarks that are associated with treatment resistance.…”

Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies

“…PEG has been used for various 3D culturing and tissue engineering applications. For example, PEG has been cultured with breast cancer cells and CAFs to evaluate drug resistance through pathways associated with tumour-stromal interactions (107,108). In another study, Caiazzo et al found that PEG can facilitate pluripotency by manipulating the microenvironment of the matrix to create a "reprogramming niche" that promotes MET and increased epigenetic remodeling capable of shifting the somatic cell fate (109).…”

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“…In particular, we focus on self-assembly strategies that have been engineered to overcome the challenges presented by animal models and current 3D in vitro models. Readers are referred to the following reviews for complementary information [ 8 , 9 , 10 ].…”