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.