Abstract
Cancer is considered one of the most predominant diseases in the world and one of the principal causes of mortality per year. The cellular and molecular mechanisms involved in the development and establishment of solid tumors can be defined as tumorigenesis. Recent technological advances in the 3D cell culture field have enabled the recapitulation of tumorigenesis in vitro, including the complexity of stromal microenvironment. The establishment of these 3D solid tumor models has a crucial role in personalized medicine and drug discovery. Recently, spheroids and organoids are being largely explored as 3D solid tumor models for recreating tumorigenesis in vitro. In spheroids, the solid tumor can be recreated from cancer cells, cancer stem cells, stromal and immune cell lineages. Organoids must be derived from tumor biopsies, including cancer and cancer stem cells. Both models are considered as a suitable model for drug assessment and high-throughput screening. The main advantages of 3D bioprinting are its ability to engineer complex and controllable 3D tissue models in a higher resolution. Although 3D bioprinting represents a promising technology, main challenges need to be addressed to improve the results in cancer research. The aim of this review is to explore (1) the principal cell components and extracellular matrix composition of solid tumor microenvironment; (2) the recapitulation of tumorigenesis in vitro using spheroids and organoids as 3D culture models; and (3) the opportunities, challenges, and applications of 3D bioprinting in this area.
Highlights
Cancer remains one of the most predominant diseases in the world in the 21st century, affecting millions of patients per year (Roy and Saikia, 2016)
The main objective of this review is to explore the cellular and molecular composition of solid tumor microenvironment, the recapitulation of tumorigenesis and drug assessment using spheroids and organoids, and the opportunities and challenges of 3D bioprinting in this field
The stromal cells are represented by endothelial cells, mesenchymal stem/stromal cells (MSCs), fibroblasts, and macrophages (Wu and Dai, 2017; O’Loghlen, 2018)
Summary
Cancer remains one of the most predominant diseases in the world in the 21st century, affecting millions of patients per year (Roy and Saikia, 2016). These cells are denominated as “tumor stroma” and, together with the extracellular matrix (ECM), oxygen levels and pH, constitute the tumor microenvironment (Briest et al, 2012; Hirata and Sahai, 2017). This complex interaction between tumor and non-tumor cells leads to an altered metabolism and ECM production. The better understanding of tumor microenvironment is a key challenge to address, contributing to the development of new drugs and treatments (Valkenburg et al, 2018) In this context, 3D cell culture has gained space in literature due to its advantages compared with “classical” 2D cell culture. Cell culture platforms of tumor spheroids and organoids start to be adapted as a model for drug assessment and high-throughput screening (HTS) (Kondo et al, 2019; Heredia-Soto et al, 2020; Renner et al, 2020)
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