Precision Medicine and Pancreatic Cancer

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

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

gemcitabine
Precision Medicine
Pancreatic Neoplasms
Deoxycytidine Kinase
Radiation Oncology
Fluorouracil
Radiotherapy
Therapeutics
Ribonucleotide Reductases
Proteins
Survival
Disease-Free Survival
Biomarkers
Logistic Models
Immunohistochemistry
Regression Analysis

Keywords

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

ASJC Scopus subject areas

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

Cite this

Farrell, J. J., Moughan, J., Wong, J. L., Regine, W. F., Schaefer, P., Benson III, A. B., ... Elsaleh, H. (2016). Precision Medicine and Pancreatic Cancer. Pancreas, 45(10), 1485-1493. https://doi.org/10.1097/MPA.0000000000000710
Farrell, James J. ; Moughan, Jennifer ; Wong, Jonathan L. ; Regine, William F. ; Schaefer, Paul ; Benson III, Al B ; Macdonald, John S. ; Liu, Xiyong ; Yen, Yun ; Lai, Raymond ; Zheng, Zhong ; Bepler, Gerold ; Guha, Chandan ; Elsaleh, Hany. / Precision Medicine and Pancreatic Cancer. In: Pancreas. 2016 ; Vol. 45, No. 10. pp. 1485-1493.
@article{e551ae55f03c4faf93234b5fdf1bd82b,
title = "Precision Medicine and Pancreatic Cancer",
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.",
keywords = "DCK, RRM1, RRM2, hENT1, pancreatic cancer, precision medicine",
author = "Farrell, {James J.} and Jennifer Moughan and Wong, {Jonathan L.} and Regine, {William F.} and Paul Schaefer and {Benson III}, {Al B} and Macdonald, {John S.} and Xiyong Liu and Yun Yen and Raymond Lai and Zhong Zheng and Gerold Bepler and Chandan Guha and Hany Elsaleh",
year = "2016",
month = "11",
day = "1",
doi = "10.1097/MPA.0000000000000710",
language = "English (US)",
volume = "45",
pages = "1485--1493",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

Farrell, JJ, Moughan, J, Wong, JL, Regine, WF, Schaefer, P, Benson III, AB, Macdonald, JS, Liu, X, Yen, Y, Lai, R, Zheng, Z, Bepler, G, Guha, C & Elsaleh, H 2016, 'Precision Medicine and Pancreatic Cancer', Pancreas, vol. 45, no. 10, pp. 1485-1493. https://doi.org/10.1097/MPA.0000000000000710

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

In: Pancreas, Vol. 45, No. 10, 01.11.2016, p. 1485-1493.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Precision Medicine and Pancreatic Cancer

AU - Farrell, James J.

AU - Moughan, Jennifer

AU - Wong, Jonathan L.

AU - Regine, William F.

AU - Schaefer, Paul

AU - Benson III, Al B

AU - Macdonald, John S.

AU - Liu, Xiyong

AU - Yen, Yun

AU - Lai, Raymond

AU - Zheng, Zhong

AU - Bepler, Gerold

AU - Guha, Chandan

AU - Elsaleh, Hany

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - DCK

KW - RRM1

KW - RRM2

KW - hENT1

KW - pancreatic cancer

KW - precision medicine

UR - http://www.scopus.com/inward/record.url?scp=84992345047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992345047&partnerID=8YFLogxK

U2 - 10.1097/MPA.0000000000000710

DO - 10.1097/MPA.0000000000000710

M3 - Article

VL - 45

SP - 1485

EP - 1493

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 10

ER -

Farrell JJ, Moughan J, Wong JL, Regine WF, Schaefer P, Benson III AB et al. Precision Medicine and Pancreatic Cancer. Pancreas. 2016 Nov 1;45(10):1485-1493. https://doi.org/10.1097/MPA.0000000000000710