Irvine, Calif., September 8, 2026 — Pancreatic cancer is among the deadliest major cancers, and most patients are diagnosed after it has spread. The liver is its most common destination, but treatments have been developed based on the response of tumors in the pancreas. New research suggests that cancer growing in the liver relies on a different local support system that may offer a promising treatment opportunity.
The study, led by the laboratory of UC Irvine Associate Professor Christopher Halbrook and published in Cellular and Molecular Gastroenterology and Hepatology, examined fibroblasts, cells that normally support and repair tissue. The researchers found that fibroblasts surrounding pancreatic tumors in the liver differed markedly from those surrounding primary tumors.
“The paper fundamentally shifts our understanding of metastasis by demonstrating that secondary tumors build entirely different support systems than primary tumors,” said Nina Steele, PhD, a key collaborator from the University of Cincinnati and the Pancreatic Cancer Center at Henry Ford Health.
Using advanced gene-mapping tools, the team compared individual cells from pancreatic and liver tumors created from the same cancer cells. Human tissue samples and laboratory-grown human fibroblasts isolated from UCI cancer patients helped confirm how liver support cells communicate with pancreatic cancer cells.
The analysis revealed that liver fibroblasts produce a growth signal called hepatocyte growth factor, or HGF. Pancreatic cancer cells in the liver carry unusually high levels of MET, the protein that receives the signal. This interaction helps the cancer grow and adjust its metabolism to its new surroundings.
Steele said the study connects that discovery to a possible treatment.
“What makes this work especially compelling is its immediate translational potential,” Steele said. “Blocking signaling between liver fibroblasts and cancer cells with a drug already in clinical use significantly inhibits liver tumor growth, turning a high-resolution transcriptomic discovery into an actionable, organ-specific therapeutic strategy.”
Producing reliable models of pancreatic cancer’s spread required specialized experimental work. First author Rima Singh, a UCI PhD graduate whose thesis project was centered on this work, described the challenge of developing the necessary surgical skills.
“The biggest challenge I faced during this project was mastering the liver surgeries used in the metastatic model system described in this paper,” Singh said. “These surgeries are technically demanding, requiring both a careful understanding of anatomy and precise surgical skill. I was able to work through this challenge with the guidance of our collaborator at the University of Miami, Oliver McDonald, MD, PhD, whose feedback helped me improve with each injection until the technique became reliable.”
Researchers then disrupted MET genetically and treated mice with cabozantinib, a MET-blocking drug already used for other cancers. Both approaches sharply reduced pancreatic tumor growth in the liver. The effect was stronger in the liver than in the pancreas, with most treated mice showing no visible liver tumors or only small tumor masses. The findings remain preclinical and must be evaluated in patients.
The research began with support from a UCI Anti-Cancer Challenge Pilot Award and later received funding from the Tower Cancer Research Foundation. Those early investments helped the project progress to long-term funding from the American Cancer Society, allowing the team to continue advancing this line of research.
Halbrook said the results demonstrate why researchers must study cancer not only at its original site but also in the organs to which it spreads.
“Our study identified that the specific features of the organ colonized during pancreatic metastasis convey unique pathways that can be leveraged for treatment,” Halbrook said. “Importantly, we would not have identified these vulnerabilities by studying only primary disease.”
Halbrook also sees potential implications for other cancers that commonly spread to the liver.
“However, our findings also have the potential to provide therapeutic insight into other cancers that metastasize to the liver,” Halbrook said. “Accordingly, we believe that a detailed understanding of the unique features of each organ frequently colonized during metastasis may reveal new cross-cancer treatment strategies. These findings will ultimately need to be tested in clinical trials, which we are currently planning to initiate at the Chao Family Comprehensive Cancer Center.”
Moving this discovery toward patient care will require further research, carefully designed clinical trials and sustained support from research funders and policymakers. Studying metastatic tumors where they grow may reveal overlooked weaknesses and lead to more precise treatments for patients who currently have limited options.
About the University of California, Irvine Charlie Dunlop School of Biological Sciences:
Recognized for its pioneering research and academic excellence, the Charlie Dunlop School of Biological Sciences plays a crucial role in the university’s status among the nation’s top 10 public universities, as ranked by U.S. News & World Report. It offers a broad spectrum of degree programs in the biological sciences, fostering innovation and preparing students for leadership in research, education, medicine and industry. Nestled in a globally acclaimed and economically vibrant community, the school contributes to the university’s impact as Orange County’s largest employer and a significant economic contributor. Through its commitment to exploring life’s complexities, the Dunlop School embodies the UC Irvine legacy of innovation and societal impact. For more on the Charlie Dunlop School of Biological Sciences, visit https://www.bio.uci.edu/.