Georgetown University, Lawrence Livermore National Laboratory (LLNL) scientists and collaborators have identified a protein that when removed from the body may help pancreatic cancer patients live longer.
Pancreatic cancer is one of the most lethal forms of the disease and has the lowest survival rate. Because the tumors are solid, many modern chemotherapies to destroy the tumor do not work.
The new findings, reported in the journal Gastoenterology, indicate that the protein cadherin 11, or CDH11, which is expressed by cancer-associated fibroblasts but is not found in most cells of a normal pancreas, stimulated immune tolerance to pancreatic tumors.
“Strategies to inhibit cadherin 11 or its signaling pathways might be developed for the treatment of pancreatic cancer,” said LLNL biologist Gaby Loots and a co-author of the report. Georgetown University’s Steven Beyers, the lead author of the study, has already identified a CDH11 inhibitor and is evaluating its potential to stop pancreatic tumor growth.
In mice subjects that were genetically engineered to contain pancreatic tumors, the team found that removal of the CDH11 gene significantly extended the survival rate of those mice. They also found that the main source of CDH11 were the cancer supporting fibroblasts.
“When you delete this molecule, the tumor environment seems to be more accessible to immune cells and kills more of the tumor,” Byers said. “In humans, our goal is to create an antibody or small molecule that inhibits the activity of cadherin 11.”
By blocking CDH11 action, immune cells can more readily access the cancer cells and synergize with chemotherapy to more efficiently eliminate tumor cells, Loots said.
“If we can create an antibody, then we are going to take it to the clinic and will start enrolling patients,” Byers said.
LLNL scientists Aimy Sebastian, Nick Hum and Kelly Martin also contributed to the research. The LLNL portion of the project was funded by the Laboratory Directed Research and Development program's Strategic Initiative under Elizabeth Wheeler’s leadership.
Industry partners Fluidigm and ST Cube Pharmaceuticals also contributed to the research.