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

Research output: Contribution to journalArticleAcademicpeer-review

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
JournalAnticancer Research
Volume39
Issue number7
DOIs
Publication statusPublished - 2019

Cite this

@article{d063542bbb6c4609b9945a0e688a4a51,
title = "Uridine cytidine kinase 2 as a potential biomarker for treatment with RX-3117 in pancreatic cancer*",
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.",
author = "Hassouni, {Btissame E. L.} and Jessica Infante and Giulia Mantini and Claudio Ricci and Niccola Funel and Elisa Giovannetti and Peters, {Godefridus J.}",
year = "2019",
doi = "10.21873/anticanres.13508",
language = "English",
volume = "39",
pages = "3609--3614",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "7",

}

Uridine cytidine kinase 2 as a potential biomarker for treatment with RX-3117 in pancreatic cancer*. / Hassouni, Btissame E. L.; Infante, Jessica; Mantini, Giulia; Ricci, Claudio; Funel, Niccola; Giovannetti, Elisa; Peters, Godefridus J.

In: Anticancer Research, Vol. 39, No. 7, 2019, p. 3609-3614.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Uridine cytidine kinase 2 as a potential biomarker for treatment with RX-3117 in pancreatic cancer*

AU - Hassouni, Btissame E. L.

AU - Infante, Jessica

AU - Mantini, Giulia

AU - Ricci, Claudio

AU - Funel, Niccola

AU - Giovannetti, Elisa

AU - Peters, Godefridus J.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068263497&origin=inward

U2 - 10.21873/anticanres.13508

DO - 10.21873/anticanres.13508

M3 - Article

VL - 39

SP - 3609

EP - 3614

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 7

ER -