Establishment and application of bladder cancer patient-derived xenografts as a novel preclinical platform
The prognosis and treatment of bladder cancer have hardly improved in the last 20 years, with the exception of immunotherapy using a PD-1/PD-L1 blocker, which was approved by the United States Food and Drug Administration in 2016. Hence, bladder cancer remains a debilitating and often fatal disease, and among one of the costliest cancers to treat. Preclinical models that are more representative of human cancer are urgently needed to improve our understanding of bladder cancer progression, as well as advance its diagnosis and treatment. Patient-derived xenografts (PDXs), involving the transfer of tumor fragments from individual patients into immunocompromised animals such as severe combined immunodeficient or nude mice, have been developed and utilized as a preclinical model of bladder cancer. PDX models recapitulating clinical behavior, including the drug response of several cancers, have demonstrated high predictive capacity to test standard chemotherapy regimens and to identify tumor types that might benefit from new treatments in clinical trials. However, current PDX models have limitations to their translation into current clinical trials including PD-1/PD-L1-related trials and personalized medicine. This review focuses on the advantages and disadvantages of PDX models in drug development, their application in bladder cancer, and future directions of PDX models.