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Randomized Controlled Trial
. 2016 Nov;45(10):1485-1493.
doi: 10.1097/MPA.0000000000000710.

Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach

James J Farrell  1 , Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson 3rd, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
Affiliations
Randomized Controlled Trial

Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach

James J Farrell et al. Pancreas. 2016 Nov.

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.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Overall survival for DCK protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 1
Figure 1
Overall survival for DCK protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 1
Figure 1
Overall survival for DCK protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 2
Figure 2
Overall survival for RRM1 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 2
Figure 2
Overall survival for RRM1 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 2
Figure 2
Overall survival for RRM1 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 3
Figure 3
Overall survival for RRM2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 3
Figure 3
Overall survival for RRM2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 3
Figure 3
Overall survival for RRM2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 4
Figure 4
Overall survival for p53R2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 4
Figure 4
Overall survival for p53R2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
Figure 4
Figure 4
Overall survival for p53R2 protein expression, multivariate analysis. A. All patients. B Gemcitabine Treatment Arm. C 5-FU treatment arm
See this image and copyright information in PMC

References

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