3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions

The complex microenvironment in which malignant tumor cells grow is crucial for cancer progression. The physical and biochemical characteristics of this niche are involved in controlling cancer cell differentiation, proliferation, invasion, and metastasis. It is therefore essential to understand how cancer cells interact and communicate with their surrounding tissue – the so-called tumor stroma – and how this interplay regulates disease progression. To mimic the tumor microenvironment (TME), 3D in vitro models are widely used because they can incorporate different patient-derived tissues/cells and allow longitudinal readouts, thus permitting deeper understanding of cell interactions. These models are therefore excellent tools to bridge the gap between oversimplified 2D systems and unrepresentative animal models. We present an overview of state-of-the-art 3D models for studying tumor–stroma interactions, with a focus on understanding why the TME is a key target in cancer therapy.