OU College of Medicine Researchers Make Discovery About Pancreatic Cancer Drug Resistance

One of the biggest barriers in treating pancreatic cancer is that it becomes resistant to chemotherapy and its rapid growth cannot be stopped.

Researchers at the OU College of Medicine have published a paper in Gastroenterology, a top journal in GI cancer research, identifying a protein that affects how much chemotherapy can travel into a cancer cell.

The discovery comes from the laboratory of Min Li, Ph.D., whose postdoctoral fellow Mingyang Liu, Ph.D., was the primary author on the research paper. Much of the research in Li’s laboratory focuses on a protein named ZIP4, which regulates zinc in the cells. In this study, they discovered that pancreatic cancer patients with higher levels of ZIP4 had shorter survival times.

“When we talk about pancreatic cancer, we often talk about drug resistance,” said Li, who holds the Virginia Kerley Cade Endowed Chair in Cancer Treatment. “We want to look at the causes of drug resistance – is less of the drug going into the pancreatic cancer cells, or is it getting there but it won’t do anything?”

In particular, Li’s team researched how ZIP4 reacted with a type of chemotherapy that has been used for years to treat pancreatic cancer, but provides little improvement. They discovered that in pancreatic cancer specimens with high levels of ZIP4, the protein sparked a cascade of events that kept most of the chemotherapy from getting into the cancer cells.

“It basically shuts the door and nothing can come in,” Li said.

That finding is important because if researchers can find a way to decrease the level of ZIP4, more of the chemotherapy drug can get into and kill the pancreatic cancer cells.

“It’s not going to cure pancreatic cancer, but it could give patients a better chance at longer survival,” he said.

Li’s research team was the first to discover, 12 years ago, that ZIP4 played an important role in pancreatic cancer. Since then, it has become his signature research focus. Last year, he published a paper on the role of ZIP4 in cachexia, a muscle-wasting condition that affects 80% or more of people with pancreatic cancer.

International collaborators and sophisticated technology also play a role in Li’s success. In addition to collaborators in several colleges at the OU Health Sciences Center and on OU’s Norman campus, he teams with others in Minnesota and Germany. Using mass spectrometry on the Norman campus, Li’s team can detect even trace amounts of chemotherapy concentration in a single cell.