Molecular switch that helps pancreatic cancer beat drugs identified
Washington, Jan 29 (ANI): Researchers at University of California, San Diego, have identified a molecular switch that helps pancreatic cancer become resistant to drugs.
The molecular switch steps up pancreatic cancer cell survival as well as resistance to a standard chemotherapy drug.
They have also identified alternate routes cancer cells take to avoid the effects of the therapy.
"To understand how to treat pancreatic cancer tumours, we need to better understand their circuitry and behaviour," said lead researcher Dr Andrew M. Lowy, professor of surgery and chief of surgical oncology at the UCSD School of Medicine and the Moores UCSD Cancer Centre.
RON is a signaling protein known as a tyrosine kinase, essentially a switch that turns on various activities in cells.
In a series of experiments, the researchers showed that RON sends signals that regulate the activity of genes that help tumours 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 cells to establish tumors in mice.
Those tumours were treated with gemcitabine, the most common chemotherapy drug used to treat pancreatic cancer patients.
Tumours in which RON was silenced were much more sensitive to the chemotherapy than the RON-expressing cancer cells.
About 50 percent of the tumour cells re-expressed RON. The researchers also found that the tumour cells activated other growth proteins, including epidermal growth factor receptor (EGFR), to enable them to continue to grow.
"We know that diseases such as pancreatic cancer are too complex for one drug to be effective. If we can learn to predict the results of RON-directed therapy, maybe we can combine it with an EGFR-directed therapy, for example, to take away tumour escape routes," Lowy added. (ANI)