Bladder cancer organoids as a functional system to model different disease stages and therapy response

Abstract

Bladder Cancer (BLCa) inter-patient heterogeneity is considered the primary cause of tumor reoccurrence and treatment failure, suggesting that BLCa patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancer types. In our study, we established BLCa PDO cultures from different BLCa stages. BLCa PDOs preserve the histological and molecular heterogeneity of the parental tumors, including their multiclonal genetic landscapes. BLCa PDOs consistently share key genetic alterations detected in parental tumors, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline was implemented using BLCa PDOs, testing both standard-of-care and additional FDA-approved compounds for other solid tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis was used to determine enrichment thresholds for candidate markers of therapy resistance and sensitivity. By assessing the clinical history of longitudinally sampled cases, the clonal evolution of the disease could be determined and matched with drug response profiles. In conclusion, we have developed a clinically relevant pipeline for drug response profile assessment and discovery of candidate markers of therapy resistance.

Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?

“…Since then, 3D organoid systems have attracted much attention and shown tremendous potential for modelling human cancers [ 38 , 39 , 40 , 41 ]. To date, organoids have been developed for many cancers, including colon cancer [ 42 ], gastrointestinal cancer [ 29 ], pancreatic cancer [ 43 ], prostate cancer [ 30 , 44 ], bladder cancer [ 45 , 46 ], liver cancer [ 47 ], breast cancer [ 48 ], and brain cancer [ 49 ].…”

“…PDOs are invaluable tools for translational study as well as basic research [ 27 , 59 ], with drug screening and testing of personalized treatment among the best-studied cancers [ 30 , 46 , 60 , 61 , 62 , 63 ]. In addition, PDOs are increasingly being used to investigate the mechanisms of tumorigenesis [ 64 , 65 , 66 , 67 , 68 ], the tumor microenvironment (TME) [ 69 ], infection–cancer progression [ 69 , 70 , 71 ], cancer metastasis [ 71 , 72 ], and immunological cancer research [ 69 , 70 , 73 , 74 ].…”