Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research

Abstract

Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa.

A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery

“…In particular, PC organoids exhibit several notable limitations, such as a low success rate of 15-20%, limited success from primary patient samples, primarily comprising epithelial and stromal cells with fewer tumor cells, and restricted access to clinical specimens, thereby impeding the creation of a diverse organoid bank [22][23][24][25][26].…”

“…In contrast, tumor spheroids derived from cancer cell lines or patient samples, which are often cultured using hydrogel-based methods, are pivotal for in vitro models in cancer research. They replicate complex in vivo tumor characteristics, such as multicellular architecture and mass transport barriers, making them superior to 2D models for drug testing and penetration studies [26]. Spheroids are crucial for exploring cell proliferation, metabolism, hypoxia, and tumor heterogeneity in cancer research [27].…”