Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.
Cancers. 2020 Jan 17*** epublish ***
Caroline Roelants, Catherine Pillet, Quentin Franquet, Clément Sarrazin, Nicolas Peilleron, Sofia Giacosa, Laurent Guyon, Amina Fontanell, Gaëlle Fiard, Jean-Alexandre Long, Jean-Luc Descotes, Claude Cochet, Odile Filhol
Université Grenoble Alpes, Inserm, CEA, IRIG-Biology of Cancer and Infection, UMR_S 1036, F-38000 Grenoble, France., Université Grenoble Alpes, Inserm, CEA, IRIG-Biologie à Grande Echelle, UMR 1038, F-38000 Grenoble, France., Centre hospitalier universitaire Grenoble Alpes, CS 10217, 38043 Grenoble CEDEX 9, France.