Newswise — New Brunswick, N.J., March 14, 2018 – Research by Rutgers Cancer Institute of New Jersey investigators further explores the use of the diabetes drug metformin and its impact on pancreatic cancer and finds that targeting a certain signaling pathway with this agent may be a novel strategy for the prevention and treatment of pancreatic cancer that has spread to other parts of the body. The latest findings from the work are being presented as part of a poster session at the American Association for Cancer Research Annual Meeting being held next month in Chicago.

Metformin continues to gain attention as an anti-cancer drug and/or a chemoprevention agent due to its role in blocking protein synthesis in the protein complex known as mTOR, modulating inflammatory responses, and selectively killing cancer stem cells. It is still unclear how metformin impacts pancreatic cancer progression and metastasis.

The gene product known as RET has a strong presence in pancreatic cancer and correlates to cancer spread and worse survival following surgery to remove the cancer, say the authors. RET is responsible for encoding a cell receptor involved in functions impacting cell proliferation, death and survival and was the focus of this research. Investigators examined the inhibitory effects of metformin on pancreatic cancer cell growth and spread. 

Examining molecular markers and assessing cell migration in laboratory models, researchers found that metformin treatment reduced RET’s signaling activity in certain pancreatic cancer cell lines. Furthermore, metformin treatment or silencing RET can significantly inhibit cell migration, suggesting that metformin may inhibit pancreatic cancer cell growth and spread at least partially through suppressing RET signaling activity.

“Our data indicate that targeting RET with metformin may be an attractive and novel strategy for the prevention and treatment of pancreatic cancer progression and metastasis. Completion of this study will form the basis for developing a novel clinical intervention strategy for inhibiting the growth and spread of pancreatic cancer using metformin and/or other selective RET inhibitors,” notes Xiang-Lin Tan, MD, PhD, who is the senior investigator of the work and member of the Cancer Prevention and Control Program at Rutgers Cancer Institute.  Dr. Tan, who is also an assistant professor of medicine at Rutgers Robert Wood Johnson Medical School and an assistant professor of epidemiology at Rutgers School of Public Health, notes additional studies are warranted.

Other authors on the work include: Huailong Chang, Rutgers Cancer Institute of New Jersey; Zhiyong Xiao, Beijing Institute of Pharmacology & Toxicology, Beijing, China; Tao Li, Rutgers Cancer Institute of New Jersey; Lanjing Zhang, University Medical Center of Princeton, Plainsboro; Yong Lin, Rutgers School of Public Health; and Darren Carpizo, Rutgers Cancer Institute of New Jersey.

This work was supported by a Post-Doctoral Cancer Research Fellowship from the New Jersey Commission on Cancer Research (DFHS17PPC008 to HL Chang) and a grant from the National Cancer Institute at the National Institutes of Health (K07CA190541 to XL Tan).

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