The first study to explain the molecular basis for pancreatic cancer cells becoming metastatic (spreading to other organs) points to improved methods of treating this deadly disease.

Published in the journal Nature by a multinational team led by researchers from the Hebrew University of Jerusalem, the study found that pancreatic ductal adenocarcinoma (PDA) tumors become metastatic because of changes in the processing of RNA molecules.

Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all US cancer deaths. The American Cancer Society estimates that this year, about 64,050 Americans will be diagnosed with pancreatic cancer and about 50,550 will die of it.

“Pancreatic cancer is the most aggressive cancer and less than 10 percent of the patient survive more than a few years after diagnosis,” said Prof. Rotem Karni of the Hebrew University Faculty of Medicine.

Karni’s doctoral student, Amina Jbara, led the study with participation of other members of Karni’s lab and researchers from Sheba Medical Center and Bar-Ilan University in Israel, Cornell University and Cold Spring Harbor Laboratory in the United States, and Toronto University in Canada.

Evaluating 395 PDA tumor samples, both non-metastatic and metastatic, the researchers discovered that a central protein that controls RNA processing, RBFOX2, is degraded and present in much lower levels in metastatic tissue.

“Our unique findings demonstrate that the disappearance of RBFOX2 protein causes hundreds of genes to produce RNAs and proteins in a different way, which contributes to the invasive capabilities of the cancer cells,” explained Karni.

“We found that restoring RBFOX2 to PDA metastatic cells inhibits the formation of metastases, while the elimination of RBFOX2 in non-metastatic PDA cells stimulates the formation of pancreatic cancer metastases.”

The findings point to two possible options for treatment of metastatic pancreatic cancer: either a known drug for organ transplant patients that inhibits a process affected by RBFOX2, or an RNA-based therapy that intervenes in the processing of specific RBFOX2-affected RNAs.

Both options underwent initial testing in lab mice. “We hope our findings will lead soon to new treatment for metastatic pancreatic cancer,” said Jbara.