Next generation patient derived tumor organoids.

Patient-derived tumor organoids (PDTOs) have emerged as exceptional pre-clinical models as they preserved, in most of the cases, the mutational landscape and tumor-clonal heterogeneity of the primary tumors. Despite being extensively used in disease modelling as well as in precision medicine for drug testing and discovery, they still have some limitations. The main limitation is that during their establishment they lose all components of the tumor microenvironment (TME) which are known modulators of tumor response to therapeutic treatment as well as disease progression. In this review we address the effects of different players of the TME such as immune cells, fibroblasts, endothelial cells and the extracellular matrix composition on tumor behavior and response to treatment as well as the different culture and co-culture strategies that could improve PDTOs value as pre-clinical models leading to the development of next generation PDTOs.