Rausch, Magdalena
Weiss, Andrea
Achkhanian, Joanna
Rotari, Andrei
Nowak-Sliwinska, Patrycja
Article History
Received: 1 December 2019
Revised: 4 April 2020
Accepted: 23 April 2020
First Online: 22 May 2020
Ethics approval and consent to participate
: No ethics approval has been filed for this project. Human clear-cell renal cell carcinoma cell lines A498, Caki-1, and 786-O were purchased at ATCC. Human embryonic non-cancerous HEK-293T cells were purchased in ATCC and generously donated by Dr. Dormond (CHUV, Lausanne, Switzerland) and human immortalised endothelial cells’ ECRF24 by Prof. AW Griffioen (Angiogenesis Laboratory, UMC Amsterdam). Normal human dermal fibroblast adult (NHDFα) cells were purchased from Vitaris (Baar, Zug, Switzerland).
: Not applicable.
: All data generated or analysed during this study are included in this published article and its Supplementary information files. The following are available online at the <i>British Journal of Cancer</i> website; Fig. InternalRef removed: sensitivity to sunitinib treatment of sunitinib-naive and sunitinib pre-treated RCC cells and dose–response curves for all selected drugs, Fig. InternalRef removed: data and model verification methods implemented to ensure the accuracy and reliability of model-based predictions in Search 1, Fig. InternalRef removed: excerpt of the optimisation process in RCC cell lines and ECRF24 cells to define a specific low-dose combination, Fig. InternalRef removed: the network of the targeted proteins by the ODC, Fig. InternalRef removed: maintenance of ODC activity following chronic or discontinued sunitinib treatment, Fig. InternalRef removed: efficacy of the ODC treatment as a function of the nutrient supply, Fig. InternalRef removed: efficacy of the ODC treatment in heterotypic 3D co-cultures, Fig. InternalRef removed: induced abnormalities of cellular morphology after treatment, Fig. InternalRef removed: treatment- and time-dependent alterations of the cell cycle and evaluation of necrotic events, Fig. InternalRef removed: full-length unprocessed western blot results of MAPK and p21 in RCC cell lines after 2 h of treatment, Fig. InternalRef removed: full- length unprocessed western blot results of MAPK and p21 in RCC cell lines after 24 h of treatment; Table InternalRef removed: selected drugs and their targets, Table InternalRef removed: characteristics of the cell lines used, Table InternalRef removed: cross-validation of all RCC-specific ODCs; Videos InternalRef removed: 3D co-culture spheroid formation containing A498-ST cells.
: P.N.S. and A.W. are the inventors on pending (EP19199136) and issued (WO2015136061A3) patents on drug combinations.
: This research was funded by Novartis Foundation of Medical-Biological Research (17A003 to P.N.S.).