Pancreatic cancer is a disease with a very poor survival rate. One reason is because it is notoriously difficult to spot in the early stages, but even when it is diagnosed early, fewer than a third of patients survive. Now, a new study may help explain why pancreatic cancer is so deadly.
The study, which is published in the journal Genes and Development, suggests a gene called ATDC – also known as TRIM29 – plays a key role in helping pre-invasive pancreatic tumors progress to a metastatic state where cancer cells travel to other parts of the body.
Senior author Dr. Diane M. Simeone, director of the Pancreatic Cancer Center at the University of Michigan Comprehensive Cancer Center in Ann Arbor, says:
“We know that patients with the earliest stage of pancreatic cancer have a survival rate of only 30%. This suggests that even in that very early stage of invasive cancer there are already cells that have spread to distant parts of the body.”
The National Cancer Institute estimate there were 46,420 new cases of pancreatic cancer in the US in 2014 and 39,590 deaths from the disease. Pancreatic cancer cases represent 2.8% of all new cancer cases among Americans and 6.8% of cancer deaths.
The team already knew that ATDC is involved in nearly 90% of pancreatic cancers and promotes growth and spread of tumors. What was not clear was how. Dr. Simeone says their finding sheds some new light on this area.
For the study, the team used mice bred to develop pancreatic cancer similar to that which arises in humans. They also studied samples of pancreatic cancer tissue and pre-invasive pancreatic lesions.
They found ATDC was expressed in a group of pre-invasive cells and also helped develop pancreatic cancer stem cells – a small group of cells in the pancreatic tumor that spurs its growth and spread.
They also discovered that ATDC appears to be involved in helping cancer cells change state – a process called “epithelial-to-mesenchymal transition,” or EMT, which results in cells being more loosely associated, allowing them to migrate more easily.
Therefore, they suggest ATDC encourages a tumor’s invasiveness and spread in the early course of pancreatic cancer.
The authors conclude that their findings are evidence of a new molecular pathway for promoting EMT in the development of pancreatic cancer, with ATDC being a “proximal regulator of EMT.”
There are currently no drugs that address this molecular pathway and the researchers propose ATDC could be a strong target. They are already working on a way to do this by creating a 3D structure that they can use as a model for drug development.
However, Dr. Simeone says it is important to focus on pancreatic cancer, for which new treatment options are desperately needed. The cancer is set to become the second leading cause of cancer death in the US by 2030, she notes.
Meanwhile, Medical News Today recently learned how “organoids” are set to transform pancreatic cancer research. Writing in the journal Cell, researchers describe how they developed a 3D organoid culture system for growing both normal and cancerous pancreatic cells in the lab.
The technique will help scientists see what is happening at molecular level to drive this deadly disease and look for new drug targets.