Patient-derived tumor organoids: advances, applications, and future directions in biomedical research

Patient-derived tumor organoids (PDTOs) have become a key tool in cancer and translational oncology because they are physiologically relevant, 3D <i>in vitro</i> systems that preserve the genetic, epigenetic and phenotypic features of patient tumors. PDTOs generated from primary, metastatic surgical resection or biopsy material fill the gap between 2D cultures and animal models. PDTOs have been shown to be more accurate for mimicking disease and treatment response. This review outlines the principles and protocols for PDTO production, characterization and validation with a focus on standardization and reproducibility. PDTOs have been widely applied in oncology and increasingly applied into translational pipelines to model tumor biology, predict therapeutic response, and guide precision medicine strategies. They have shown to be predictive for drug response and are being used as personalized therapeutic avatars. However, several challenges remain, including the limited representation of tumor microenvironment, inter-laboratory variability in protocol adaptation and ethical concerns related to biobanking and data governance. New technologies such as immunological and stromal co-culture systems, organoid-on-chip technologies and multi-omic integration will enhance the use of PDTOs in biomedical research.