Research from the University of Michigan Comprehensive Cancer Centre helps explain why pancreatic cancer is so lethal, with fewer than a third of patients surviving even early stage disease. The researchers found a gene known to be involved in nearly 90% of pancreatic cancers promotes cancer growth and spread. The gene, ATDC, plays a key role in how a tumour progresses from a pre-invasive state to an invasive cancer to metastatic cancer.
"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," says study author Dr Diane M Simeone, director of the Pancreatic Cancer Centre at the University of Michigan Comprehensive Cancer Centre. "This study sheds important light on what it is about pancreatic cancer that makes it so aggressive early in the game," she adds.
Researchers used a mouse model to replicate pancreatic cancer as it appears in humans. They also studied pancreatic cancer tissue samples and samples of pre-invasive pancreatic lesions. They found ATDC was expressed in a subset of the pre-invasive cells and played a role in the development of pancreatic cancer stem cells, the small number of cells in a tumour that fuel its growth and spread. This suggests that ATDC promotes a tumour's invasiveness and spread early in the course of disease.
The researchers suspect that ATDC may be a potent drug target. No drugs currently exist to target this pathway in part because researchers do not understand the crystal structure of the protein. Simeone's team, working with the University of Michigan Centre for Structural Biology has made crystals of the protein and begun to create a three-dimensional structure that they can use as a model for drug development.
Preliminary data suggests that ATDC may also play a role in other cancer types, including bladder, ovarian, colorectal and lung cancers and multiple myeloma. But, Simeone notes, it’s particularly critical to find new treatment options for pancreatic cancer.
[link url="http://www.mcancer.org/news/archive/what-makes-pancreatic-cancer-so-aggressive-new-study-sheds-light"]University of Michigan Health System release[/link]
[link url="http://genesdev.cshlp.org/content/29/2/171.abstract?sid=36a4e1f7-eb16-4e28-94d2-dab47ce1ddf7"]Genes and Development abstract[/link]