Establishment of bladder cancer spheroids and cultured in microfluidic platform for predicting drug response.

Abstract

Cisplatin-containing combination chemotherapy has been used as the standard treatment for bladder cancer patients at advanced stage. However, nearly 50% of patients are nonresponders. To guide the selection of more effective chemotherapeutic agents, a bladder cancer spheroids microfluidic drug sensitivity analysis system was established in this study. Bladder cancer spheroids were established and successfully cultured in a customized microfluidic device to assess their response to different chemotherapeutic agents. The in vitro drug sensitivity results were also compared to patient-derived xenograft (PDX) models and clinical responses of patients. As a result, bladder cancer spheroids faithfully recapitulate the histopathological and genetic features of their corresponding parental tumors. Furthermore, the in vitro drug sensitivity outcomes of spheroids (n = 8) demonstrated a high level of correlation with the PDX (n = 2) and clinical response in patients (n = 2). Our study highlights the potential of combining bladder cancer spheroids and microfluidic devices as an efficient and accurate platform for personalized selection of chemotherapeutic agents.