• Posted July 8, 2024

Scientists Find Way to Reverse Chemo Resistance in Pancreatic Cancer Patients

Pancreatic cancer is particularly aggressive and difficult to treat, partly because it’s often resistant to chemotherapy.

Researchers now think they know why chemo struggles to work against pancreatic cancer – and how to reverse that resistance.

It turns out that the physical stiffness of the tissue around the cancer cells makes chemo less effective, researchers reported July 4 in the journal Nature Materials.

“We found that stiffer tissue can cause pancreatic cancer cells to become resistant to chemotherapy, while softer tissue made the cancer cells more responsive to chemotherapy,” senior researcher Sarah Heilshorn, a professor of materials science and engineering at Stanford University, said in a news release.

“These results suggest an exciting new direction for future drug development to help overcome chemoresistance, which is a major clinical challenge in pancreatic cancer,” she added.

The study focused on pancreatic ductal adenocarcinoma, which accounts for 90% of pancreatic cancer cases. This form of cancer starts in the cells lining the ducts of the pancreas.

In these cancers, the tissue becomes notably stiffer, acting as a physical block that prevents chemo from reaching cancer cells, researchers said.

To figure out what is happening, researchers designed tissue in the lab that mimicked the properties of both pancreatic tumors and healthy pancreas tissues. They then used this tissue to culture cells drawn from pancreatic cancer patients.

“We created a designer matrix that would allow us to test the idea that these cancerous cells might be responding to the chemical signals and mechanical properties in the matrix around them,” Heilshorn said.

The researchers found that two things caused pancreatic cancer to become resistant to chemo – stiffer tissue and high amounts of hyaluronic acid, a substance that helps stiffen the tissue.

Hyaluronic acid interacts with cellular tissue through a receptor called CD44. Researchers found they could make tissue softer and more responsive to chemo if they blocked the CD44 receptor.

“We can revert the cells back to a state where they are sensitive to chemotherapy,” Heilshorn said. “This suggests that if we can disrupt the stiffness signaling that’s happening through the CD44 receptor, we could make patients’ pancreatic cancer treatable by normal chemotherapy.”

The research team continues to investigate the CD44 receptor, as well as the chain of events that follows after the receptor is activated in a cancerous cell.

The researchers are also working to improve their cell culture model, so that it can be used to predict how chemo and other cancer therapies will work in specific patients.

“When we design chemotherapies, we should be testing our cultures in matrices that are relevant to a patient,” Heilshorn said. “Because it matters – the way cells respond to drugs depends on the matrix that’s around them.”

More information

The American Cancer Society has more about pancreatic cancer.

SOURCE: Stanford University, news release, July 4, 2024