Hutchinson Center researcher contributes major breakthrough to pancreas cancer studies

By Clay Holtzman, Hutchinson Center science writer

When I sat down with Sunil Hingorani for an interview in mid-March, I had no idea he had just made a major breakthrough in pancreas cancer research.

In retrospect, I should have half expected it, considering Hingorani has a long history of advancing research of this deadly disease. He developed the primary model to study pancreas disease in the lab, and he also helped identify why pancreas tumors are resistant to chemotherapy. Hingorani’s story, I would learn, had a new chapter.

Dr. Sunil Hingorani

“If you want to talk about how you go from a fundamental discovery to a novel approach for treatment that is now beginning to establish in patients it can work, that would be this story,” said Hingorani, who heads the Center’s pancreas cancer research program.

I quickly found myself on the edge of my seat, hanging on to every word as Hingorani explained what his research has uncovered and how those discoveries set the stage for his latest breakthrough.

“What a pancreas cancer does is extremely insidious,” Hingorani began. “First, it calls in cells from the body early in it process and encourages them to lay down the same proteins involved in scar formation. So by the time that it becomes a tumor, it is a hard, fibrous ball with the tumor cells protected inside it.

“Next, the cancer calls in immune cells from the body, but only the ones that will shut down the immune system, and those contribute to its shield.

“The third thing that happens is because of that dense scar tissue and the immune cells that it calls in, the pressure in the tumor becomes very high, and that crushes the blood vessels inside and closes them shut. Now you have a tumor that is a perfect sanctuary from the rest of the body. Every drug that has ever been tried in a patient has failed, even though when we study the cancer cells in the lab and pour the drugs on  them, they die.”

Before Hingorani’s research, all of that information was unknown to scientists. But I was about to learn how Hingorani and colleagues were taking that knowledge and leveraging it for a treatment strategy.

“We’ve learned that if you use a special enzyme to dissolve those proteins that contribute to that pressure-forming matrix, those blood vessels inside the tumor will open before your eyes. Now you can get drugs in at will, and when you do that, the tumors are completely vulnerable and they die,” Hingorani said.

Called an enzymatic therapy, this new treatment has significantly increased the length of survival in genetically engineered mice, and now early clinical trials in humans are under way.

It will be years before Hingorani can determine if this new strategy is safe and effective in humans, but you can bet I won’t be the only one interested in how this story ends.

To learn more about the Hutchinson Center’s comprehensive approach to studying pancreas cancer, visit our pancreas cancer disease page.