Abstract 1192: Establishment and characterization of a new patient-derived renal cell carcinoma xenograft panel
Authors: Susanne Flechsig, Annika Wulf-Goldenberg, Christian Schmees, Burkhard Jandrig, Jörg Hennenlotter, Jens Bedke, Martin Schostak, Andrew Crockford, Marco Gerlinger, James Larkin, Charles Swanton, Zoltan Szallasi, Iduna Fichtner, Jens Hoffmann
Journal: Cancer Research (2014)

Abstract Objective: Patients with advanced kidney cancer have a poor prognosis. The majority of patients develops treatment resistance towards Standard of Care (SoC) drugs within months. The successful development of novel personalized therapies depends on the availability of preclinical models with high clinical relevance. Our aim was to establish a panel of patient-derived renal cell carcinoma xenograft models for translational research. Methods: Specimens from primary and metastatic renal cell carcinoma tumors from consenting patients were collected after surgery and transplanted subcutaneously to immunodeficient mice within 24 hours. Tumor engraftment was followed for an initial period of up to 4 months. Successful engrafted patient-derived tumors were subsequently passaged to further mice. HE stained tumor sections were histopathologically examined to assess morphological concordance between patient tumor and PDX model. Renal cell carcinoma marker expression was determined by immunohistochemistry. Stably growing xenografts were tested for sensitivity towards SoC drugs, such as Avastin, Sunitinib, Sorafenib and Everolimus. Response to treatment was evaluated by comparing growth inhibition of treated in relation to untreated tumors. Primary tumors and the derived xenografts are currently under characterization for common oncogenic mutations using the Illumina TruSeq Amplicon Cancer Panel. Results: Nearly 200 tumor samples were transplanted since 2011. To date, 30% were successfully engrafted in immunodeficient mice and further patient-derived tumors are presently under establishment. Engraftment rates of samples from pT3 and pT4 tumors were higher (34%) than those from pT1 and pT2 tumors (12%). Two tumor samples which were pre-treated before surgery engrafted so far (11%). We show that specific tumor histology and renal cell carcinoma marker expression remained preserved over the passages. The drug sensitivity testings revealed a heterogeneous response to SoC treatments with Sunitinib (79% significant growth inhibition) and Everolimus (64%) as most effective treatments in the PDX models. Avastin showed a significant growth inhibition in 57% whereas Sorafenib was effective in 36% of the RCC models. We are furthermore presenting the individual gene mutation status of each RCC model. Conclusions: Our newly established patient-derived renal cell carcinoma panel provides a novel tool for the investigation of mechanisms of drug resistance and sensitivity in kidney cancer, biomarker research and the development of new therapeutic approaches. Citation Format: Susanne Flechsig, Annika Wulf-Goldenberg, Christian Schmees, Burkhard Jandrig, Jörg Hennenlotter, Jens Bedke, Martin Schostak, Andrew Crockford, Marco Gerlinger, James Larkin, Charles Swanton, Zoltan Szallasi, Iduna Fichtner, Jens Hoffmann. Establishment and characterization of a new patient-derived renal cell carcinoma xenograft panel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1192. doi:10.1158/1538-7445.AM2014-1192