Tumor organoid models in precision medicine and investigating cancer-stromal interactions

Tumor development and progression require chemical and mechanical cues derived from cellular and non-cellular components in the tumor microenvironment, including the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells. Therefore, it is crucial to develop tissue culture models that can mimic in vivo cancer cell-ECM and cancer-stromal cell interactions. Three-dimensional (3D) tumor culture models have been widely utilized to study cancer development and progression. A recent advance in 3D culture is the development of patient-derived tumor organoid (PDO) models from primary human cancer tissue. PDOs maintain the heterogeneity of the primary tumor, which makes them more relevant for identifying therapeutic targets and verifying drug response. Other significant advances include development of 3D co-culture assays to investigate cell-cell interactions and tissue/organ morphogenesis, and microfluidic technology that can be integrated into 3D culture to mimic vasculature and blood flow. These advances offer spatial and temporal insights into cancer cell-stromal interactions and represent novel techniques to study tumor progression and drug response. Here, we summarize the recent progress in 3D culture and tumor organoid models, and discuss future directions and the potential of utilizing these models to study cancer-stromal interactions and direct personalized treatment.