Precision Medicine and Pancreatic Cancer

James J. Farrell, Jennifer Moughan, Jonathan L. Wong, William F. Regine, Paul Schaefer, Al B. Benson, John S. Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objectives There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. Methods Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine. Tumor DCK, RRM1, RRM2, and p53R protein expressions were analyzed using a tissue microarray and immunohistochemistry and correlated with treatment outcome (overall survival and disease-free survival) by unconditional logistic regression analysis. Results There were 229 patients eligible for analysis from both the 5-fluorouracil and gemcitabine arms. Only RRM2 protein expression, and not DCK, RRM1, or p53R2 protein expression, was associated with survival in the gemcitabine treatment arm. Conclusions Despite limited data from other nonrandomized treatment data, our data do not support the predictive value of DCK, RRM1, or p53R2. Efforts should focus on human equilibrative nucleoside transporter 1 and possibly RRM2 as valid predictive markers of the treatment response of gemcitabine in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1485-1493
Number of pages9
JournalPancreas
Volume45
Issue number10
DOIs
StatePublished - Nov 1 2016

Keywords

  • DCK
  • RRM1
  • RRM2
  • hENT1
  • pancreatic cancer
  • precision medicine

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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  • Cite this

    Farrell, J. J., Moughan, J., Wong, J. L., Regine, W. F., Schaefer, P., Benson, A. B., Macdonald, J. S., Liu, X., Yen, Y., Lai, R., Zheng, Z., Bepler, G., Guha, C., & Elsaleh, H. (2016). Precision Medicine and Pancreatic Cancer. Pancreas, 45(10), 1485-1493. https://doi.org/10.1097/MPA.0000000000000710