Precision Medicine and Pancreatic Cancer: A Gemcitabine Pathway Approach.

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.

• Authors: James J Farrell, 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
• Journal: Pancreas (Pancreas) Vol. 45 Issue 10 Pg. 1485-1493 (11 2016) ISSN: 1536-4828 [Electronic] United States
• PMID: 27748721 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antimetabolites, Antineoplastic
• Equilibrative Nucleoside Transporter 1
• Tumor Suppressor Proteins
• Deoxycytidine
• Gemcitabine

Topics

• Antimetabolites, Antineoplastic
• Deoxycytidine (analogs & derivatives)
• Equilibrative Nucleoside Transporter 1
• Humans
• Pancreatic Neoplasms
• Precision Medicine
• Tumor Suppressor Proteins
• Gemcitabine