Pancreatic cancer is a significant cause of cancer-related death, standing in fourth place globally. It is also the twelfth most common cancer type worldwide, with around 458,918 new cases diagnosed in 2018. Unfortunately, the prognosis for patients with metastatic disease is poor, with a five-year survival rate of less than 3% after diagnosis. Early detection of pancreatic cancer is rare and challenging due to the absence of distinct symptoms until the later stages. As a result, approximately 80% of patients receive their diagnosis after the cancer has already spread.
Researchers from Sheba, in collaboration with the Hebrew University of Jerusalem, Bar-Ilan University, Cornell University, and Toronto University, conducted a comparative study on 400 non-metastatic pancreatic tumors and metastatic growth cells. The study yielded significant findings regarding the mechanisms of pancreatic cancer metastasis. Although the DNA mutations that cause healthy pancreatic cells to turn cancerous have been known for some time, how pancreatic cancer cells metastasize and invade other organs remained unclear.
A breakthrough cancer research study revealed that changes in RNA molecule processes within cells are associated with the transformation of non-metastatic tumors into metastatic growths. Specifically, researchers discovered that a protein called RBFOX2, which plays a crucial role in controlling RNA processing, undergoes degradation and vanishes in metastatic pancreatic cancer cells. This degradation of RBFOX2 alters the production of hundreds of genes, leading to the creation of RNA and proteins in a different manner that contributes to the invasiveness of the cells.
The study also found that the reintroduction of RBFOX2 to metastatic cells can inhibit the formation of metastases, while its suppression can stimulate the formation of pancreatic cancer metastases. The disappearance of RBFOX2 affects a group of genes that control the organization of the cell cytoskeleton, which is crucial for the mobility and invasive ability of the cells.
Importantly, a drug called Azathioprine has been identified as a potential therapeutic option for addressing the mobility and invasiveness of pancreatic cancer cells. The drug targets a protein responsible for controlling the organization of the cell cytoskeleton, which is crucial for the mobility and invasive ability of the cells.
“If we use this drug, we could inhibit metastases in cells that have lost RBFOX2,” explained Prof. Rotem Karni, an expert in molecular cancer biology at the Faculty of Medicine at the Hebrew University. The discovery of the potential of azathioprine offers hope for treating this deadly form of cancer.
These promising results offer a new potential avenue for pancreatic cancer treatment, which could significantly improve the prognosis for patients with this deadly disease. The study represents a significant milestone in cancer research, providing hope for improved outcomes for pancreatic cancer patients in the future.