The Osteosarcoma Tumor Microenvironment: From Cellular Interactions to Advanced Preclinical Models

Abstract

Simple Summary Osteosarcoma (OS) is a rare and aggressive bone cancer that mainly affects children and adolescents. Developing new and effective treatments is challenging because OS is a complex disease that interacts with the tumor microenvironment. Preclinical models are essential for studying tumor biology, growth, metastasis, and responses to therapy before treatments are tested in patients. Several models, including 3D cell cultures, organoids, and animal models, are used to reproduce different aspects of OS. However, each model has specific advantages and limitations, and no single model can completely reproduce the complexity of the tumor. The tumor microenvironment, which includes immune cells, bone cells, blood vessels, and an extracellular matrix, plays an important role in tumor progression and treatment resistance. This review summarizes the main preclinical models from spheroids to PDXs used to study OS and their ability to reproduce the tumor microenvironment, highlighting their importance for improving research and developing more effective therapies.