Advances in In Vitro Modeling of Cancer-Stromal Interactions: From Fundamental Insights to Translational Applications

Accurate in vitro modeling of the tumor microenvironment (TME) is essential for advancing our understanding of cancer biology and for developing effective anti-cancer therapeutics. Context-dependent and patient-specific, the dynamic interactions between cancer cells and stromal elements significantly affect tumor progression and treatment response. Recent advances in biomaterials, microdevices, and molecular analysis techniques have facilitated the development of in vitro tumor models that better replicate these cancer-stromal interactions. In turn, these models have deepened the understanding of cancer biology, leading to the discovery of new prognostic markers and establishing preclinical platforms that more reliably predict clinical outcomes. However, challenges persist in fully capturing the immense complexity of the TME and translating these models for real clinical impact. In this review, key design principles for creating physiologically relevant tumor models are first described, then the latest advances in tumor modeling that have contributed to new biological insights and progress in drug development are discussed.