Cell receptor may lead to new 'biomarker' for pancreatic cancer

http://www.acor.org/news/whatsnew.html?item_id=5636
Cell receptor may lead to new 'biomarker' for pancreatic cancer

Published: Jul 01, 2007

CINCINNATI -- A research team led by University of Cincinnati (UC)
scientists has identified a potential biological target for pancreatic
cancer, a finding they say could help scientists better understand -- and
eventually treat -- the disease that kills more than 33,000 people each
year.

In laboratory studies led by Andrew Lowy, MD, and Susan Waltz, PhD, the
Cincinnati researchers found that a specific cell receptor -- known as the
RON receptor tyrosine kinase -- was ?overexpressed,? or increased, in
pancreatic cancer cells. This, says Waltz, suggests the receptor may also
contribute to the disease?s development.

The RON receptor has been found to be active in several cancers --
including breast cancer -- but its role in pancreatic cancer was unknown.
This is one of the first studies, published in the July 1, 2007, issue of
the journal Cancer Research, to report a link between the RON receptor and
pancreatic cancer.

Receptor tyrosine kinases are proteins on the cell surface used to
activate specific body functions -- for example cell growth and migration.

?A normal pancreas has very low levels of RON, but our study showed that
as tumors progress, so does the level of RON expression in the pancreas
cells -- and those overexpressed levels were maintained in ?metastases,?
the areas that the tumors spread to,? explains Waltz, associate professor
and director of the oncology research program in UC?s surgery department.

The team found that the RON receptor was active in 93 percent of what is
known as pancreatic intraepithelial neoplasia, an early form of pancreatic
duct cancer. In addition, the receptor was present in 79 percent of
primary pancreatic cancers and 83 percent of metastatic cancers.

UC researchers believe the RON receptor?s signaling pathways could be a
key factor contributing to pancreatic cancer progression. Waltz says if
the receptor could be blocked, it would give drug developers a new target
for RON-directed therapies that are more effective in treating this deadly
disease.

?When cells became invasive,? Waltz said, ?we saw higher levels of RON
expression that correlated with the aggressive nature of this disease and
cancer metastasis. Clearly, this signaling pathway is associated with
pancreatic cancer and merits further investigation.?

A relatively rare but difficult disease to treat, pancreatic cancer will
affect about 37,000 Americans in 2007. According to the National Cancer
Institute, overall survival for the disease is only about 4 percent --
often because the disease spreads before it can be clinically detected.

In the December 2006 issue of Cancer Research, Waltz reported that the RON
receptor can also be involved in breast cancer. Based on those earlier
findings, she and Lowy wanted to know if the receptor was also expressed
in pancreatic cancer -- an aggressive, highly metastatic cancer -- and
whether it played a role in disease development.

For the UC study, researchers used the protein HGFL (hepatocyte growth
factor-like) to activate the RON receptor. Although stimulating the RON
receptor had no effect on pancreatic cell growth, blocking it with
targeted antibodies killed more cancer cells than did the standard
treatment drug gemcitabine (gem-SITE-uh-bean) alone.

?Our findings suggest that combining antibodies that block the RON
receptor and the standard chemotherapy drugs might stop progression of
pancreatic cancer more effectively,? says Waltz. ?RON could be a promising
molecular target for future cancer drug development.?

Waltz stresses, however, that additional preclinical research is needed
before RON receptor blockers become available for human testing



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