Introduction: The selection of effective therapeutic agents is critical to improve the life prognosis of patients with renal cell carcinoma (RCC). In this study, we established 3-dimensional (3D) tumor organoids from freshly resected RCC tumors and tested tyrosine kinase inhibitors (TKIs), targeted therapeutics for metastatic RCC, as a drug testing model for development of potential personalized therapy for RCC patients.
Methods: Surgical tumor specimens were obtained from 20 patients with RCC. 3D tumor organoids were developed ex vivo from freshly resected RCC tumors and their histopathological and molecular characteristics were evaluated using histological staining and whole exome sequencing (WES). Using cell viability assay, we determined the therapeutic efficacy of TKIs in RCC tumor organoids.
Results: We found that RCC tumor organoids recapitulate the histological architecture of the primary tumor. Using WES, we identified strong concordance of primary tumors and corresponding tumor organoids at genetic level. We demonstrated that RCC tumor organoids respond differently to targeted therapeutics showing patient-specific sensitivity to the treatment.
Conclusions: Our results identify concordance of genetic aberrations in primary RCC and corresponding tumor organoids, and demonstrate that tumor organoid models allow ex vivo drug testing of tumor samples obtained from RCC patients to predict a potential clinical response to targeted therapeutics.
Source of Funding: The present study was supported by a research grant from the Department of Urology, Division of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (grant no. CH29017; August, 2018).
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