Login to Access Video or Poster Abstract: MP88-17
Sources of Funding: The Wade Thompson Family Foundation, The Sidney Kimmel Center for Prostate and Urologic Cancers, Support Grant P30 CA008747, Urology Care Foundation, Society of Urologic Oncology

Introduction

Upper tract urothelial carcinomas (UTUC) are treated similarly to urothelial carcinoma of the bladder (UCB). UTUC demonstrates a more aggressive clinical course which may be explained by significant differences in mutational frequencies between UTUC and UCB that were reported using a customized exon capture sequencing assay (the MSK-IMPACTTM assay). A major limitation in the advancement of UTUC field is the lack of appropriate models. The objective of this study was to develop and evaluate preclinical models that would recapitulate treatment response observed in patients.

Methods

35 surgical specimens from nephroureterectomy of patients with UTUC were implanted into immunocompromised NOD-SCID IL2Rg?/? (NSG) mice. The histological and the genomic characterization of patient tumors and PDXs were examined by a board certified pathologist and MSK-IMPACTTM assay, respectively. Cell lines were also established to assess histologic and genetic fidelity. Chemosensitivity of PDX models was assessed using a 4-week cycle of gemcitabine/cisplatin (or carboplatin) administration and analysis of tumor growth was performed using a two-way ANOVA test.

Results

12 patient-derived xenograft (PDX) models were established with a success rate of 34% (12/35) and a 14% (3/21) success in developing cell lines. Both models were highly reflective of their original tumors in terms of histology and genomic characteristics as noted in Figure 1 and 2. For a representative PDX, chemosensitivity experiments identified gemcitabine/carboplatin as a potentially effective combination, which was also used in the clinical scenario with a therapeutic response.

Conclusions

We developed a cohort of stable PDX models and cell lines for UTUC that maintains the genetic characteristics of the patient’s initial tumor. The continued development of these models may facilitate personalized medicine strategies in the treatment of UTUC.

Funding

The Wade Thompson Family Foundation, The Sidney Kimmel Center for Prostate and Urologic Cancers, Support Grant P30 CA008747, Urology Care Foundation, Society of Urologic Oncology