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Cancer Prevention Research
Cancer Prevention Research
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Review

Repurposing of Metformin and Aspirin by Targeting AMPK-mTOR and Inflammation for Pancreatic Cancer Prevention and Treatment

Wen Yue, Chung S. Yang, Robert S. DiPaola and Xiang-Lin Tan
Wen Yue
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
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Chung S. Yang
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
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Robert S. DiPaola
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
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Xiang-Lin Tan
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
1Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; 2Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy; and 3Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey
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DOI: 10.1158/1940-6207.CAPR-13-0337 Published April 2014
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Abstract

Pancreatic cancer, as the fourth leading cause of cancer-related deaths, carries a poor prognosis with a median survival of 6 months and a dismal 5-year survival rate of 3% to 5%. These statistics highlight an urgent need for novel chemopreventive and therapeutic strategies for this malignancy. Metformin and aspirin have been explored as two emerging cancer chemoprevention agents for different types of cancers, including pancreatic cancer. Here, we review the effects of both metformin and aspirin on pancreatic tumorigenesis and their potential actions in pancreatic cancer. Special attention is paid to their effects on the important signaling pathways of pancreatic cancer development as well as possible mechanisms for synergy between these two agents. For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways. For aspirin, the major mechanism is the anti-inflammatory action through the inhibition of COX-1/COX-2 and modulation of the NFκB or STAT3 pathway. In addition, aspirin may activate AMPK, and both agents may affect Notch, Wnt/β-catenin, and other signaling pathways. The combination of metformin and aspirin will provide additive and possibly synergistic effects for the prevention and treatment of pancreatic cancer. Cancer Prev Res; 7(4); 388–97. ©2014 AACR.

  • Received September 24, 2013.
  • Revision received January 27, 2014.
  • Accepted January 28, 2014.
  • ©2014 American Association for Cancer Research.
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Cancer Prevention Research: 7 (4)
April 2014
Volume 7, Issue 4
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Repurposing of Metformin and Aspirin by Targeting AMPK-mTOR and Inflammation for Pancreatic Cancer Prevention and Treatment
Wen Yue, Chung S. Yang, Robert S. DiPaola and Xiang-Lin Tan
Cancer Prev Res April 1 2014 (7) (4) 388-397; DOI: 10.1158/1940-6207.CAPR-13-0337

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Repurposing of Metformin and Aspirin by Targeting AMPK-mTOR and Inflammation for Pancreatic Cancer Prevention and Treatment
Wen Yue, Chung S. Yang, Robert S. DiPaola and Xiang-Lin Tan
Cancer Prev Res April 1 2014 (7) (4) 388-397; DOI: 10.1158/1940-6207.CAPR-13-0337
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  • Article
    • Abstract
    • Introduction
    • Inflammation and Pancreatic Tumorigenesis
    • The Effects of Metformin on Pancreatic Tumorigenesis
    • The Effects of Aspirin on Pancreatic Tumorigenesis
    • Pharmacodynamic and Pharmacokinetic for Metformin and Aspirin
    • Mechanisms by Which Metformin and Aspirin Inhibit mTOR and Inflammation
    • Additional Signaling Pathways Targeted by Metformin and Aspirin
    • Evidence for Synergy between Metformin and Aspirin against Pancreatic Cancer
    • Conclusions and Perspectives
    • Disclosure of Potential Conflicts of Interest
    • Grant Support
    • Dedication
    • Acknowledgments
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