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Lankenau Institute for Medical Research investigators uncover new therapeutic target for pancreatitis, a risk factor for pancreatic cancer

November 21, 2017 Research News

November is Pancreatic Cancer Awareness Month: A new study from LIMR scientists unveils the cellular mechanisms that appear to promote pancreatitis and pancreatic cancer

A new study from the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, demonstrated that elevated levels of a particular protein led to symptoms characteristic of pancreatitis, and when coupled with the presence of a genetic mutation, led to the development of pancreatic cancer. Their results could lead the way to a new therapeutic target to treat pancreatitis, a known risk factor for pancreatic cancer.

In the U.S., about 53,000 people will be diagnosed with pancreatic cancer in 2017, according to the American Cancer Society. Unfortunately, the disease has a one-year survival rate of only 20 percent, and a five-year survival rate of just seven percent.

The LIMR researchers centered their studies on the RNA-binding protein Human antigen R (HuR) that, in normal circumstances, helps maintain cells throughout the body in a healthy state. But when healthy cells are stressed from environmental insults (e.g., smoking, alcohol consumption), or in the case of tumor cells, from chemotherapy or nutrient depletion, HuR levels increase dramatically and regulate genes that promote an inflammatory microenvironment leading—the LIMR researchers discovered—to chronic pancreatitis, a disease in which the pancreas becomes inflamed.

After unveiling the link between HuR-mediated inflammation and pancreatitis-like symptoms, the scientists then set out to try to determine the cellular mechanism that leads from pancreatitis to pancreatic cancer.

“We found in our preclinical studies that when the pancreas is inflamed due to elevated HuR and a genetic mutation in the K-ras gene is present, the incidence of pancreatic ductal adenocarcinoma increased more than three-fold when compared to the presence of the K-ras mutation alone,” said Professor Janet Sawicki, PhD, deputy director of LIMR and senior investigator of the study. “We found that HuR overexpression alone does not cause cancer, but when it is paired with an oncogenic initiating event such as a K-ras mutation, the incidence of pancreatic cancer increases.”

Weidan Peng, PhD, research assistant professor in Dr. Sawicki’s lab and the lead author of the study, noted: “These are exciting findings, because they offer proof-of-concept of a novel therapeutic target for pancreatitis—namely, mediation of HuR expression in the pancreas—that could, in turn, reduce the risk of pancreatic cancer.”

The researchers’ study, “Elevated HuR in pancreas promotes a pancreatitis-like inflammatory microenvironment that facilitates tumor development,” was published in a recent edition of the biomedical journal Molecular and Cellular Biology. Other authors of this paper include LIMR researchers Narumi Furuuchi, Ludmila Aslanukova and Yu-Hung Huang, as well as collaborators from the Sidney Kimmel Cancer Center at Thomas Jefferson University, and the University of Kansas Medical Center.

The research was funded by the National Institutes of Health, the W.W. Smith Charitable Foundation, the Mary Halinski Pancreatic Cancer Research Fund, and the Lankenau Medical Center Foundation.

About Main Line Health

Founded in 1985, Main Line Health is a not-for-profit health system serving Philadelphia and its western suburbs. Main Line Health's commitment—to deliver advanced medicine for treating and curing disease, playing an important role in prevention and disease management as well as training physicians and other health care providers—reflects our intent to be the region's premier choice for clinical care, research, and education. A team of more than 10,000 employees, 3,000 nurses and 2,000 physicians care for patients throughout the Main Line Health System.

At Main Line Health's core are four of the region's most respected acute care hospitals—Lankenau Medical Center, Bryn Mawr Hospital, Paoli Hospital and Riddle Hospital—as well as one of the nation's premier facilities for rehabilitative medicine, Bryn Mawr Rehabilitation Hospital.

Main Line Health also includes Mirmont Treatment Center for drug and alcohol recovery; Main Line Health HomeCare & Hospice, which includes skilled home health care, hospice and home infusion services; Main Line Health Centers, primary and specialty care, lab and radiology, and other outpatient services located in Broomall, Collegeville, Concordville, Exton, King of Prussia and Newtown Square; Lankenau Institute for Medical Research, a biomedical research organization; and Main Line HealthCare, one of the region's largest multispecialty physician networks.

Main Line Health is the recipient of numerous awards for quality care, and service, including U.S. News & World Report's Best Hospitals, System Magnet® designation; the nation's highest distinction for nursing excellence and the Mid-Atlantic Alliance for Performance Excellence (MAAPE) Excellence Award. Main Line Health is committed to creating an environment of diversity, respect, equity, and inclusion, has proudly received awards in this area and has embraced the American Hospital Association's #123forEquity Pledge to Act to eliminate disparities in care. We are dedicated to advancing patient-centered care, education, and research to help patients stay healthy and live their best lives.

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About Lankenau Institute for Medical Research

Lankenau Institute for Medical Research (LIMR) is a nonprofit biomedical research institute located on the campus of Lankenau Medical Center and is part of Main Line Health. Founded in 1927, LIMR's mission is to improve human health and well-being. Faculty and staff are devoted to advancing innovative new approaches to formidable medical challenges, including cancer, cardiovascular disease, gastrointestinal disorders and autoimmune diseases, such as diabetes and arthritis. LIMR's principal investigators conduct basic, preclinical and translational research, using their findings to explore ways to improve disease detection, diagnosis, treatment and prevention. They are committed to extending the boundaries of human health through technology transfer and training of the next generation of scientists and physicians.