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Promising target for new pancreatic cancer treatments discovered

Date:
November 5, 2010
Source:
University of North Carolina School of Medicine
Summary:
For almost three decades, scientists and physicians have known that a gene called the KRAS oncogene is mutated in virtually all pancreatic cancers, making it an important target for scientists looking for a way to stop the growth of pancreatic cancer tumors. Medical researchers have now narrowed the focus of this scientific quest to a protein called RGL2.

One of the most frustrating problems faced by doctors who treat pancreatic cancer is the lack of effective therapeutic options. More than 38,000 people in the United States die of the disease each year, and new drugs and treatments are desperately needed.

For almost three decades, scientists and physicians have known that a gene called the KRAS oncogene is mutated in virtually all pancreatic cancers, making it an important target for scientists looking for a way to stop the growth of pancreatic cancer tumors. The problem is that the KRAS gene triggers cancer cell growth in numerous ways, through multiple cell signaling pathways, and scientists have had difficulty determining which one will be the most promising to block -- an important first step in designing a drug for use in patients.

In a paper published November 5 in the Journal of Biological Chemistry, a team from UNC Lineberger Comprehensive Cancer Center has narrowed the focus of this scientific quest to a protein called RGL2.

According to Channing Der, PhD, who led the research, "The pathway we talk about this paper is one we have investigating for more than five years. We think it is an attractive target for achieving what has, to date, been impossible: making a KRAS-blocking drug."

Der, who is a distinguished professor of pharmacology and UNC Lineberger member, says, "We are particularly optimistic about RGL2 because we know that this protein is a critical component of KRAS signaling to another class of proteins called Ral GTPases, which are essential for the growth of almost all pancreatic tumors."

Working with Jen Jen Yeh, MD, assistant professor of surgery, Sharon Campbell, PhD, professor of biochemistry and biophysics, Der and his laboratory team were able to demonstrate that RGL2 is overexpressed -- not only in pancreatic tumor cells grown in the laboratory but also in tissue taken from pancreatic cancer patients.

According to Der, "Many ideas work in the artificial environment of cell culture but not in real cancer patients. Our work with actual pancreatic tumor tissue makes us optimistic that our new understanding of this pathway can lead to a therapeutic impact for the cancer patient."

Other members of the UNC Lineberger team include postdoctoral fellow Dominico Vigil, PhD, Timothy Martin and Falina Williams.

The research was supported by grants from the National Institutes of Health, UNC Lineberger's National Cancer Institute Special Program of Research Excellence (SPORE) in Gastrointestinal Cancer, the Emerald Foundation, the American Cancer Society, the Kimmel Foundation, the American College of Surgeons and by the University Cancer Research Fund.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. Vigil, T. D. Martin, F. Williams, J. J. Yeh, S. L. Campbell, C. J. Der. Aberrant Overexpression of the Rgl2 Ral Small GTPase-specific Guanine Nucleotide Exchange Factor Promotes Pancreatic Cancer Growth through Ral-dependent and Ral-independent Mechanisms. Journal of Biological Chemistry, 2010; 285 (45): 34729 DOI: 10.1074/jbc.M110.116756

Cite This Page:

University of North Carolina School of Medicine. "Promising target for new pancreatic cancer treatments discovered." ScienceDaily. ScienceDaily, 5 November 2010. <www.sciencedaily.com/releases/2010/11/101105101400.htm>.
University of North Carolina School of Medicine. (2010, November 5). Promising target for new pancreatic cancer treatments discovered. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2010/11/101105101400.htm
University of North Carolina School of Medicine. "Promising target for new pancreatic cancer treatments discovered." ScienceDaily. www.sciencedaily.com/releases/2010/11/101105101400.htm (accessed September 2, 2014).

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