Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy

Osteosarcoma (OS), a prevalent malignant bone tumor, has seen limited progress in treatment efficacy and patient outcomes over decades. Recent insights into the tumor microenvironment (TME) have revealed its crucial role in tumor progression and therapeutic resistance, particularly in OS. This review offers a comprehensive exploration of the OS microenvironment, meticulously dissecting its crucial components: the mesenchymal stromal TME, the immune microenvironment, hypoxia-induced adaptations, and the impact of the physical microenvironment. By demonstrating how these elements collectively drive tumor proliferation, immune evasion, and invasion, this review explores the intricate molecular and cellular dynamics at play. Furthermore, innovative approaches targeting the OS microenvironment, such as immunotherapies, are presented. This review highlights the importance of the TME in OS progression and its potential as a source of novel therapeutic strategies, offering new hope for improved patient outcomes.