Btissame El Hassouni1, Jessica Infante1, Giulia Mantini1, Claudio Ricci2, Niccola Funel3, Elisa Giovannetti1,3,4, Godefridus J Peters5. 1. Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands. 2. Department of Civil and Industrial Engineering, University of Pisa, Pisa, Italy. 3. Cancer Pharmacology Lab, AIRC Start Up Unit, Pisa, Italy. 4. Fondazione Pisana per la Scienza, Pisa, Italy. 5. Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands gj.peters@amsterdamumc.nl.
Abstract
BACKGROUND/AIM: The novel cytidine analog RX-3117, which is activated by uridine-cytidine kinase 2 (UCK2), shows encouraging activity in pancreatic and bladder cancer Phase IIa studies. In this study we highlight the potential role of UCK2 as a biomarker for selecting patients for RX-3117 treatment. PATIENTS AND METHODS: The online genomics analysis and visualization platform, R2, developed by the Oncogenomics department at the AMC (Amsterdam, The Netherlands) was used for in silico UCK2-mRNA correlation with overall survival of pancreatic cancer patients, while UCK2 protein expression was evaluated by immunohistochemistry on pancreatic tumor formalin-fixed-paraffin-embedded sections from independent pancreatic cancer patients. mRNA expression was also determined for SUIT-2, PANC-1 and PDAC-3. Lastly, the drug sensitivity to RX-3117 was investigated using the Sulforhodamine-B cytotoxicity assay. RESULTS: The in silico data showed that a high UCK2-mRNA expression was correlated with a shorter overall survival in pancreatic cancer patients. Moreover, UCK2 protein expression was high in 21/25 patients, showing a significantly shorter mean. Overall Survival (8.4 versus 34.3 months, p=0.045). Sensitivity to RX-3117 varied between 0.6 and 11 μM. CONCLUSION: Pancreatic cancer cells are sensitive to pharmacologically achievable RX-3117 concentrations and UCK2 might be exploited as a biomarker for patient treatment selection. Copyright
BACKGROUND/AIM: The novel cytidine analog RX-3117, which is activated by uridine-cytidine kinase 2 (UCK2), shows encouraging activity in pancreatic and bladder cancer Phase IIa studies. In this study we highlight the potential role of UCK2 as a biomarker for selecting patients for RX-3117 treatment. PATIENTS AND METHODS: The online genomics analysis and visualization platform, R2, developed by the Oncogenomics department at the AMC (Amsterdam, The Netherlands) was used for in silico UCK2-mRNA correlation with overall survival of pancreatic cancerpatients, while UCK2 protein expression was evaluated by immunohistochemistry on pancreatic tumorformalin-fixed-paraffin-embedded sections from independent pancreatic cancerpatients. mRNA expression was also determined for SUIT-2, PANC-1 and PDAC-3. Lastly, the drug sensitivity to RX-3117 was investigated using the Sulforhodamine-Bcytotoxicity assay. RESULTS: The in silico data showed that a high UCK2-mRNA expression was correlated with a shorter overall survival in pancreatic cancerpatients. Moreover, UCK2 protein expression was high in 21/25 patients, showing a significantly shorter mean. Overall Survival (8.4 versus 34.3 months, p=0.045). Sensitivity to RX-3117 varied between 0.6 and 11 μM. CONCLUSION:Pancreatic cancer cells are sensitive to pharmacologically achievable RX-3117 concentrations and UCK2 might be exploited as a biomarker for patient treatment selection. Copyright