A breakthrough in the study of deadly pancreatic cancer

Hebrew University researchers have discovered the molecular mechanism that allows pancreatic cancer to metastasize and become fatal. The discovery offers new treatment methods for the first time

Pancreatic cancer is considered the deadliest of all types of cancer, and a few percent of patients survive more than a few years with the disease. Currently, there is no effective treatment against pancreatic cancer which is usually detected in its metastatic stage. Although in the last decade several genetic changes (mutations) have been discovered that contribute to the development of pancreatic cancer, to date no genetic changes have been found that make the tumor invasive and metastatic - the deadly stage of cancer.

In a new study published today (Wednesday) in the prestigious journal Nature, led by doctoral student Amina Jabara from the research team of Prof. Rotem Karni, an expert in the molecular biology of cancer at the Faculty of Medicine of the Hebrew University, the researchers compared approximately four hundred pancreatic cancer tumors in the non-metastatic stage to tumor cells metastases and discovered that changes in the processing of the RNA molecules in the cell and not genetic changes in the DNA, are what cause the tumor to become metastatic.

The researchers discovered that a central protein that controls RNA processing called RBFOX2 is broken down and disappears in metastases. The disappearance of RBFOX2 causes hundreds of genes to produce RNA and proteins in a different way that contributes to the invasion of the cells. The researchers showed that restoring RBFOX2 to metastatic cells inhibits the formation of metastases, while its silencing stimulates the formation of pancreatic cancer metastases. The disappearance of RBFOX2 specifically affects a group of genes that control the organization of the cell skeleton and are important for the motility and invasive ability of the cells. The studies showed that by using a drug that inhibits the activity of this group of genes and is currently used to treat organ transplant patients, it is possible to delay the formation of pancreatic cancer metastases. In addition, by genetic intervention in the RNA processing process of the target genes of RBFOX2, the researchers showed that it is possible to eliminate the metastatic ability of pancreatic cancer cells taken from patients so that they cannot form metastases when transplanted into mice.

Prof. Carney adds: "The research findings explain for the first time the molecular (non-genetic) basis for pancreatic cancer cells becoming metastatic and offer two ways to continue treatment: a known drug that inhibits a protein in an important pathway for invasion that is affected by RBFOX2, or an RNA-based therapy that intervenes in the process of processing the RNA "A on which RBFOX2 affects to treat metastatic pancreatic cancer".     

Research teams and doctors from Sheba Medical Center and Bar Ilan University in Israel and Cornell University, Toronto University, Cold Spring Harbor Labs in the USA and Canada are partners in the research.

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