UCI Study Uncovers New Target to Halt Pancreatic Cancer Spread to the Liver

Pancreatic cancer has long been a grim diagnosis, largely because most patients only learn they have it after the disease has already spread. The liver is the most common destination for those rogue cells, yet almost all therapies have been designed with the primary tumor in mind.

Now a UCI‑led investigation suggests the story is more complicated – the tumor’s new neighborhood in the liver brings its own set of helpers, and those helpers might be vulnerable.

The work, headed by UC Irvine Associate Professor Christopher Halbrook and published in Cellular and Molecular Gastroenterology and Hepatology, zeroed in on fibroblasts – the ordinary‑looking cells that usually patch up tissue. By comparing fibroblasts that hug pancreatic tumors inside the pancreas with those that surround the same cancer after it settles in the liver, the scientists saw a stark difference.

“It really flips our thinking about metastasis,” says Nina Steele, PhD, a key collaborator from the University of Cincinnati and Henry Ford Health. “Secondary tumors don’t just copy what the primary did; they build a whole new support crew.”

Using high‑resolution gene‑mapping tools, the team examined individual cells from matched pancreatic‑and‑liver tumors. Human tissue samples and lab‑grown fibroblasts taken from UCI patients helped confirm the findings in a more realistic setting.

The reveal? Liver fibroblasts crank out a protein called hepatocyte growth factor (HGF). Meanwhile, pancreatic cancer cells that have migrated to the liver load up on the MET receptor, which happily catches HGF’s signal. This HGF‑MET conversation essentially tells the cancer, “Hey, you’re in a new home – grow!” and nudges the cells to rewire their metabolism accordingly.

What’s striking is that a drug already approved for other cancers – cabozantinib, which blocks MET – can interrupt that chatter. In mouse models, genetically disabling MET or treating the animals with cabozantinib dramatically shrank liver tumors, often leaving the organ tumor‑free or with only tiny nodules. The effect was noticeably stronger in the liver than in the pancreas.

First author Rima Singh, a UCI PhD graduate, recalls the steep learning curve: “I spent weeks mastering the liver‑injection surgeries needed for this model. It was tough, but with guidance from Oliver McDonald at the University of Miami, I finally got the technique to work reliably.”

Funding for the project started modestly, with a UCI Anti‑Cancer Challenge Pilot Award, then grew thanks to the Tower Cancer Research Foundation and a substantial grant from the American Cancer Society. Those dollars let the team keep pushing the discovery toward a clinical test, which Halbrook says could begin at the Chao Family Comprehensive Cancer Center soon.

Halbrook stresses that looking at cancer where it actually lives – in this case, the liver – can expose hidden weaknesses that would be missed if we only study the primary tumor. He also speculates that similar organ‑specific pathways might exist for other cancers that love to settle in the liver, opening the door to cross‑cancer treatment strategies.

In short, the study points to a concrete, drug‑ready target for a disease that desperately needs new options. The next step will be careful clinical trials, sustained funding, and a willingness from the broader research community to focus on metastatic sites as much as on the original tumor.