Development of a 3D tumor model based on decellularized matrix using high-throughput approaches

Precision medicine aims to develop 3D tumor models to validate new therapies and investigate disease mechanisms by isolating the extracellular matrix as a foundation for recreating tumors <i>in vitro</i>. The use of decellularized tumor matrices offers a promising and versatile platform for <i>in vitro</i> cancer research and therapeutic testing. The tumor microenvironment (TME) is the surrounding milieu of cancerous tissues and contains an intricate network of extracellular matrix (ECM) components and signaling proteins that regulate tumorigenesis, invasion, and metastasis. However, the decellularization techniques process can be disruptive and often damage essential macromolecules and proteins, potentially compromising the restoration of a biologically relevant microenvironment during recellularization. This review explores the most relevant macromolecules and proteins within the TME, emphasizing their roles in tumors and metastasis. Here, the potential of reinstating these components into decellularized tumor scaffolds to enhance their biological relevance and functionality is highlighted. Key macromolecules, including collagen, fibronectin, hyaluronic acid (HA), and laminin, are discussed alongside the contributions of proteins such as integrins, matrix metalloproteinases (MMPs), and growth factors to ECM remodeling, cell adhesion, migration, and proliferation. The strategic reintroduction of these elements will improve the recellularization process and create more realistic TME models. These improved models hold promise for cancer research, medication discovery, and therapeutic testing, providing a deeper understanding of tumor biology and enabling the development of more effective treatment strategies.