Uridine Cytidine Kinase 2 as a Potential Biomarker for Treatment with RX-3117 in Pancreatic Cancer

Anticancer Res. 2019 Jul;39(7):3609-3614. doi: 10.21873/anticanres.13508.


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.

Keywords: Pancreatic cancer; RX-3117; UCK2; uridine cytidine kinase.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Female
  • Humans
  • Male
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • RNA, Messenger / metabolism
  • Uridine Kinase / genetics
  • Uridine Kinase / metabolism*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Messenger
  • fluorocyclopentenylcytosine
  • Cytidine
  • UCK2 protein, human
  • Uridine Kinase