In vitro three-dimensional modeling for prostate cancer

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Although 5-year survival rate is close to 100% for localized tumors, the disease often progresses to the metastatic stage, with a 70% drop in survival. Several experimental models have been implemented to understand the determinants of PCa progression. In vitro approaches are typically based on cell culture in plastic vessels, mainly because of high reproducibility and simplicity. However, their significance is limited by the inability to mimic the complexity of PCa pathophysiology. On the other hand, in vivo models can better recapitulate the human disease, but they impose significant logistic and experimental demand and lack the fine control of experimental variables. Advanced three-dimensional (3D) biomimetic systems have been developed as a bridge to interconnect traditional in vitro and in vivo strategies. These systems include spherical cancer models, such as tumorspheres and organoids; natural or synthetic matrices and scaffolds; microfluidic devices; bioreactors; and ex vivo explants. All these models have been applied to study different phases of PCa progression, encompassing tumor initiation, invasion of the surrounding tissues, angiogenesis, subsequent intravasation and extravasation, cancer cell dormancy and establishment of metastases in distant organs. The relative complexity and flexibility of 3D models allow them to recapitulate peculiar in vivo features, including aspects of original tissue architecture, kinetics of tumor growth, interaction with multiple cell types and extracellular components of the surrounding stroma, and therapeutic response in a more relevant environment. Such characteristics make these models suitable for addressing questions related to the biology of PCa and advancing our knowledge on the molecular, cellular, and tissue mechanisms that underlie PCa progression and treatment.