How Tumor Environments Shape Pancreatic Cancer — and New Paths for Treatment

PANCREATIC CANCER HAS a reputation for slow-growing tumors that stubbornly resist chemotherapy. But what if improving treatment depends on understanding the disease habitat?

Using a cutting-edge technique, Ashiq Masood, MD, pictured above, is beginning to describe how the environment around a tumor differs based on where it’s located in the body and how it might influence the way cancer behaves.

“Tumors are not one-size-fits-all,” said Masood, associate professor of medicine at the IU School of Medicine. “What happens when an invasive species comes in? It changes the dynamics. Each part of it has different types of cells doing different jobs.”

Mapping these ecotypes could lead to more personalized therapies — critical in a disease where the 5-year patient survival rate is only about 13%.

Take a primary tumor: It’s sheathed in a dense layer of tissue created by fibroblasts and in an environment starved of oxygen. Cancer also reprograms immune cells to block the body’s defenses, making it a challenge for standard treatments to be effective. One potential solution, Masood said, is targeting fibroblasts with drugs to shrink tumors before surgery.

Once pancreatic cancer begins to spread, that changes. Tumors that invade the nearby liver thrive in oxygen-rich environments, allowing cancer cells to divide rapidly. Crucially, their metabolism shifts — to burn sugar as an energy source. For these patients, therapies could target the pathways cancer uses to fuel growth.

Yet Masood thinks the most promising area may be the tumor’s “invasive edge”— a conflict zone where immune cells battle cancer. “We are finding a huge tug of war,” he said.

Unfortunately, the immune system’s efforts aren’t always efficient and can wind up helping their foe. Neutrophils can kill cancer cells but also be hijacked to help tumors grow. B cells, which typically produce antibodies, can also be similarly reprogrammed. Understanding this terrain could lead to smarter immune-based therapies.

It’s a new way of seeing cancer — and a new path toward hope.

To help advance innovative pancreatic cancer research and the development of new therapies at IU Simon Comprehensive Cancer Center, please contact Liz Standiford at estandi@iu.edu.