Researchers Show Aspirin Boosts Production of an Anti-Inflammatory That Inhibits Tumor Growth

Jacqueline Mitchell (BIDMC Communications) 617-667-7306, jsmitche@bidmc.harvard.edu

MARCH 12, 2019

The naturally occurring resolvins enhance the immune system’s ability to clear the body of tumor cells

BOSTON – About half of all Americans 45 years and older and older take a low dose of aspirin daily either to reduce the risk of a second heart attack or stroke or prevent a first one, a practice dating back to the 1940s. Since then, strong epidemiological evidence has also suggested that a daily dose of aspirin, an anti-inflammatory drug, may reduce the risk of cancer by up to 30 percent. However, daily aspirin also increases the risk of bleeding, limiting its use as a cancer preventing medication.

In a new study published this week in the Proceedings of the National Academy of Sciences, scientists led by Dipak Panigrahy, MD, of the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) and Charles N. Serhan, PhD, DSc, director of the Center of Experimental Therapeutics and a member of the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women’s Hospital, demonstrate a unique new mechanism by which aspirin inhibits cancer.

Working with multiple preclinical cancer models, the team demonstrated that aspirin both blocks production of compounds that promote inflammation and triggers the production of naturally occurring anti-inflammatory factors produced by the human body called resolvins. Resolvins were first discovered by co-corresponding author Serhan and colleagues at the Brigham in 2002.

In  study, aspirin-triggered resolvins inhibited primary tumor growth by enhancing the immune system’s ability to clear the body of tumor cell debris. (In a 2017 study, Panigrahy, Serhan and colleagues showed that debris from cancer cells killed by chemotherapy can promote new tumor growth.) When the scientists treated the tumor-bearing mice with aspirin-triggered resolvins alone in the absence of aspirin, they found it inhibited primary tumor growth in a variety of tumor types and at low concentrations.

“We were surprised at the potency of the aspirin-triggered resolvins in blocking tumor growth – they exhibited anti-tumor activity at much lower concentrations than aspirin in preclinical models,” said Panigrahy, who is also Assistant Professor in the Department of Pathology at Harvard Medical School. “These results have pivotal implications for cancer therapy and chemoprevention. Aspirin-triggered resolvins may be harnessed to mimic aspirin’s potent anti-tumor activity without running the risk of aspirin-related toxicity.”

“These are exciting results with potential implications for care and treatment,” said Serhan. “As our understanding of resolvins deepens, novel functions and applications are emerging that will merit clinical investigation.”

In addition to Panigrahy and Serhan, authors include co-lead authors Molly M. Gilligan and Allison Gartung; and, Megan L. Sulciner, of Beth Israel Deaconess Medical Center; Paul C Norris, of Brigham and Women’s Hospital; Vikas P. Sukhatme of Emory University School of Medicine; Diane R. Bielenberg, of Boston Children’s Hospital; Sui Huang, of Institute for Systems Biology; and, Mark W. Kieran, of Dana-Farber Cancer Institute (currently at Bristol-Myers Squibb).

This work was supported by the National Cancer Institute (R01 01CA170549, R0CA 148633, 5P01 GM095467); the Credit Unions Kids at Heart Team; the Stop and Shop Pediatric Brain Tumor Fund; Alex’s Lemonade Stand; Molly’s Magic Wand for Pediatric Brain Tumors; the Markoff Foundation Art-in-Giving Foundation; the Kamen Foundation; Jared Branfman Sunflowers for Life; and the Joe Andruzzi Foundation.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.