INDIANAPOLIS -- Two Indiana University researchers have been awarded a multi-year, $3.2 million grant to develop and improve therapies for pancreatic cancer, the fourth leading cause of cancer death in the United States.
Mark R. Kelley, Ph.D., Betty and Earl Herr Professor of Pediatric Oncology Research, and Melissa L. Fishel, Ph.D., assistant research professor of pediatrics, both at the IU School of Medicine, were awarded a 5-year grant (CA167291) from the National Cancer Institute of the National Institutes of Health. The two Indiana University Melvin and Bren Simon Cancer Center researchers will focus on investigating the signaling pathways and molecular mechanisms that contribute to pancreatic tumor progression and resistance to therapy.
Signaling pathway describes a group of molecules in a cell that work together to control one or more cell functions, such as cell division or cell death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated until the last molecule is activated and the cell function is carried out. Abnormal activation of signaling pathways can lead to cancer.
In their laboratory research, Drs. Kelley and Fishel plan to block a protein, redox factor 1 (Ref-1), which is crucial to regulating pancreatic tumor growth and metastasis. They will use a protein inhibitor that Dr. Kelley and colleagues developed that has shown promise in the lab in blocking Ref-1.
"We will study a particular protein, Ref-1, that we believe is involved in signaling between the tumor and the tumor's environment," Dr. Fishel said. "We hope to better understand how this protein signals and functions in the tumor microenvironment as well as in the tumor cells. We're hoping that if we can inhibit the function of Ref-1, we can blunt the tumor's ability to live."
Researchers have been learning that a tumor's microenvironment plays a significant role in the life and death of a tumor.
"We're realizing that it's not just the tumor that has to be treated," Dr. Kelley added. "You have to treat the tumor and the surrounding support structure, its microenvironment. Because pancreatic cancer is hard to treat, we think Ref-1 is a viable target both in the tumor and the microenvironment. If we can hit it in both places, it's a double win."
This latest pancreatic cancer project builds on Dr. Kelley's ongoing research into using inhibitors to prevent cancer cells from repairing the damage caused by anti-cancer therapies.
Drs. Kelley and Fishel will collaborate with other IU Simon Cancer Center researchers, which Dr. Kelley referred to as an example of "team science." The others include internationally recognized cancer researcher Murray Korc, M.D., the Myles Brand Professor of Cancer Research at the IU School of Medicine and director of the Indiana University-Purdue University Indianapolis Pancreatic Cancer Signature Center. The signature center, an IUPUI designation that represents a research strength and focus in an area that is not commonly studied, brings together nearly 50 basic scientists and clinicians who work to improve outcomes for pancreatic cancer patients.
The research team also includes Theresa Guise, M.D., Jerry and Peggy Throgmartin Professor of Oncology, and Mircea Ivan, M.D., Ph.D., assistant professor of medicine, both at the IU School of Medicine. Dr. Guise is an expert on tumor microenvironment and metastatic disease, while Dr. Ivan is an expert in hypoxia, a condition in which there is a decrease in the oxygen supply. Pancreatic tumors are hypoxic, which makes them more aggressive and difficult to treat.
There is a need for new therapies for pancreatic cancer patients because current treatments typically only extend a person's life for six to 10 weeks. Only 6 percent of people with the disease survive more than five years after diagnosis. According to the National Cancer Institute, there will be an estimated 45,220 new cases of pancreatic cancer and 38,460 deaths from the disease in 2013.
"Our hope and goal is to change the standard of care because it's not working," Dr. Fishel said. "Our hope is to bring a new therapy -- or a new one that would be used in conjunction with a current therapy -- to make inroads against this disease. Even if a new therapy doesn't kill the tumor, if it can penetrate the microenvironment to help other drugs get to the tumor, that would be beneficial."