Aspirin could boost immune response to cancer

John Murphy, MDLinx, 09/08/2015
Adding aspirin to immunotherapy could greatly improve cancer treatment, according to a new study published online September 3, 2015 in Cell.

Aspirin could halt cancer cells’ protective barrier and unleash the full power of the immune system.

The study builds on research that tumor cells are often able to evade the immune system, although how tumor cells do this is not fully understood. But prior research has found that cyclooxygenase (COX) in tumors produces prostaglandin E2 (PGE2), which is associated with enhanced cancer cell survival, growth, migration, and immunosuppression.
In this study, researchers determined that melanoma, colorectal, and breast cancers produce excess PGE2, which suppresses tumor immunity and induces inflammation associated with cancer progression.
“We’ve added to the growing evidence that some cancers produce PGE2 as a way of escaping the immune system,” said study author Caetano Reis e Sousa, DPhil, senior group leader at the Francis Crick Institute in London, U.K. “If you can take away cancer cells’ ability to make PGE2, you effectively lift this protective barrier and unleash the full power of the immune system.”
Asprin, a COX inhibitor, could stop the production of PGE2, which would prevent tumors from evading the immune system. When the researchers tested it in mice, they found that aspirin combined with an immune checkpoint blocker (anti-PD-1 monoclonal antibody) substantially slowed melanoma and colorectal cancer growth, compared with immunotherapy alone.
“Giving patients COX inhibitors like aspirin at the same time as immunotherapy could potentially make a huge difference to the benefit they get from treatment,” said Dr. Reis e Sousa. “It’s still early work but this could help make cancer immunotherapy even more effective, delivering life-changing results for patients.”

Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.

Cancer Prev Res (Phila). 2014 Feb 11. [Epub ahead of print]
Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.

1Medicine/Population Science, Rutgers Cancer Insititue of New Jersey.

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 3-5%. 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 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. Additionally, aspirin may activate AMPK, and both agents may affect Notch, Wnt/β 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.

PMID:24520038   [PubMed – as supplied by publisher]