Uridine cytidine kinase 2 as a potential biomarker for treatment with RX-3117 in pancreatic cancer*

Btissame E. L. Hassouni, Jessica Infante, Giulia Mantini, Claudio Ricci, Niccola Funel, Elisa Giovannetti, Godefridus J. Peters

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6 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3609-3614
Number of pages6
JournalAnticancer research
Volume39
Issue number7
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Pancreatic cancer
  • RX-3117
  • UCK2
  • Uridine cytidine kinase

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