UCI Researchers Spot a New Weak Spot in Liver‑Metastatic Pancreatic Cancer

Pancreatic cancer is a grim statistic for most patients—by the time it’s caught, it’s often already on a road trip to the liver. The standard treatment playbook, however, has been written for tumors still hanging out in the pancreas, not for those that have set up shop elsewhere.

That gap is what a team from the University of California, Irvine set out to fill. Led by Associate Professor Christopher Halbrook, the group zeroed in on the tiny, often‑overlooked cells that line the scaffolding of our organs: fibroblasts. These connective‑tissue cells normally help repair wounds, but they also act as a kind of neighborhood watch for cancer cells, handing out signals that can either curb or encourage growth.

What the researchers found was a bit of a plot twist. Fibroblasts that live in the liver look and act very differently from the ones that cling to a tumor in the pancreas. Using single‑cell gene‑mapping, they showed that liver fibroblasts crank out a protein called hepatocyte growth factor (HGF). In the same micro‑environment, pancreatic cancer cells have a surplus of MET receptors—the very “ears” that listen to HGF’s instructions.

When HGF meets MET, it’s like flipping a switch that tells the cancer cells to thrive in their new home, reshaping their metabolism and pushing them to multiply. “It’s a whole new support system,” says Nina Steele, PhD, a collaborator from the University of Cincinnati and Henry Ford Health, “and that means new therapeutic angles.”

Armed with that insight, the team tried a fairly straightforward strategy: block the conversation. Cabozantinib, a drug already approved for other cancers because it blocks MET, was administered to mice bearing pancreatic tumors that had metastasized to the liver. The results were striking—most treated mice showed no visible liver tumors, and any that did appear were tiny compared with untreated controls.

“The beauty of this is that we’re not inventing a brand‑new drug,” Steele notes. “We’re repurposing something that’s already in the clinic, which could shave years off the timeline to get patients the help they need.”

Getting to that point wasn’t a walk in the park. First author Rima Singh, a UCI PhD graduate, spent months mastering delicate liver‑injection surgeries to build a reliable mouse model of pancreatic metastasis. “Those surgeries felt like trying to perform a heart transplant on a hamster at first,” she laughs, “but with guidance from our collaborators at the University of Miami, it eventually clicked.”

Beyond the immediate findings, Halbrook stresses the broader lesson: “If we only study cancers where they originate, we miss the organ‑specific tricks they pick up along the way.” That idea could apply to other cancers that love the liver, such as colorectal or breast cancer.

The project got its start thanks to a UCI Anti‑Cancer Challenge Pilot Award, followed by support from the Tower Cancer Research Foundation and a larger grant from the American Cancer Society. With those funds, the team is now gearing up for the next step—clinical trials at the Chao Family Comprehensive Cancer Center to see whether the pre‑clinical promise translates to people.

In a field where survival rates have barely budged for decades, the study offers a refreshing reminder that looking at cancer from a new angle—literally, a new organ—can uncover vulnerabilities that were hiding in plain sight.