Establishment of a panel of patient-derived tumor xenograft models recapitulating molecular heterogeneity and drug response of muscle-invasive bladder tumors.

Background: Muscle-invasive bladder cancers (MIBCs) constitute a heterogeneous group of tumors with poor outcome. Recently, MIBC molecular subtyping efforts from an international consortium led to the identification of six subtypes, improving prediction of clinical outcomes and treatment responses. FGFR3 alterations (mutations and translocations), observed in 20% of MIBCs, are found mainly in the luminal papillary subtype that respond poorly to chemo- and immunotherapy. Basal tumors represent 35% of MIBCs and were shown to be better responders to chemotherapy. Here, we describe the development and characterization of patient-derived primary MIBC xenografts (PDX) belonging to these main subtypes. Methods: Bladder tumors were obtained from patients at surgery. Tumor fragments were subcutaneously engrafted into immune-compromised mice. Primary tumors and matched PDX tumors at multiple passages were analyzed regarding growth characteristics, histopathology (HE 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A24.