Patient-derived bladder cancer xenografts: a systematic review

Abstract

Patient-derived tumor xenografts (PDTXs) are said to accurately reflect the heterogeneity of human tumors. In the case of human bladder cancer, few studies are available featuring these models. The best methodology to develop and the real value of the model remain unclear. This systematic review aims to elucidate the best methodology to establish and use PDTXs to study the characteristics and behavior of human bladder tumors. The value and potential application of these models are also addressed. A comprehensive literature search was performed to identify published studies using xenograft models directly established from human bladder cancer samples into mice. A total of 12 studies were included in the final analysis. All studies differed in design; the reported take rate varied between 11% and 80%, with the implantation via dorsal incision and with matrigel obtaining the higher take rate. Advanced stage and high-grade tumors were associated with increased take rate. Xenografts preserved the original tumor identity in the establishment phase and after serial passages. Although some studies suggest a correlation between engraftment success and clinical prognosis, evidence about the association between the response of xenografts to treatment and the clinical response of the tumor of origin is still missing. All methodological approaches resulted in the establishment of tumor xenografts with preservation of the original tumor identity but variable take rate. The time needed to establish the model and propagate xenografts to a number suitable for drug testing is the main limitation of the model, along with the success rate and lack of consistency in the early passages. Comparison between tumor response in mice and clinical outcome remains to be assessed.