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Scientists show how molecular switch helps pancreatic cancer beat drugs
Date:1/28/2010

Researchers at the Moores Cancer Center at the University of California, San Diego, have found one reason that pancreatic cancer tumors are so difficult to treat with drugs. They have shown how a molecular switch steps up pancreatic cancer cell survival as well as resistance to a standard chemotherapy drug, and have identified alternate routes cancer cells take to avoid the effects of the therapy.

The findings, by a group led by Andrew M. Lowy, MD, professor of surgery and chief of surgical oncology at the UCSD School of Medicine and the Moores UCSD Cancer Center, are reported online and will appear February 1 in the journal Cancer Research. The study provides new insights into pancreatic cancer development and new potential drug targets and treatment strategies against the disease.

"To understand how to treat pancreatic cancer tumors, we need to better understand their circuitry and behavior," Lowy said.

Pancreatic cancer is a particularly deadly cancer, fast-moving and difficult to detect early. It's estimated that more than 35,000 people died from pancreatic cancer last year in the United States.

RON is a signaling protein known as a tyrosine kinase, essentially a switch that turns on various activities in cells. Previous work in Lowy's lab showed that RON is overexpressed in a majority of precancerous and pancreatic cancer cells, and could also help cells resist dying. The researchers wanted to find out what role, if any, RON played in pancreatic cancer development and progression.

In a series of experiments, the researchers showed that RON sends signals that regulate the activity of genes that help tumors cells survive, "implying RON is a potent survival signal for pancreatic cancer cells," Lowy said.

To see the effects of reducing or blocking RON activity, the team shut down RON expression in pancreatic cancer cells using a molecular technique called "gene silencing," and then used those cel
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Contact: Steve Benowitz
sbenowitz@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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