Common Cholesterol Drugs Show Promise Against Chemotherapy-Resistant Pancreatic Cancer

Christopher Halbrook, PhD, associate professor at the UC Irvine Charlie Dunlop School of Biological Sciences, Alica Michels, MD, gastroenterologist at University Hospital Ulm, Germany, and Jennifer Valerin, MD, PhD, assistant professor in the Division of Hematology and Oncology in the Department of Medicine. 

Irvine, Calif., October 22, 2026 — Pancreatic cancer can become harder to treat when tumors stop responding to chemotherapy, leaving patients and families with few options. University of California, Irvine researchers have identified a weakness that emerges as cancer cells resist a widely used chemotherapeutic, pointing to a possible new use for cholesterol-lowering statins.

Published in Gastroenterology, the study was led by the lab of Associate Professor Christopher Halbrook at the UC Irvine Charlie Dunlop School of Biological Sciences. The collaboration brought together UC Irvine's Chao Family Comprehensive Cancer Center, School of Medicine and School of Pharmacy & Pharmaceutical Sciences with University Hospital Ulm in Germany; the University of Glasgow and Glasgow Royal Infirmary in the United Kingdom; the University of Chicago; UC San Diego; and Caris Life Sciences.

The team studied pancreatic cancer cells as they became resistant to gemcitabine, a mainstay chemotherapy, and tested drugs that disrupt how cells make and use essential chemicals. Resistant cells became especially sensitive to statins. In mice, the statin pitavastatin inhibited the growth of gemcitabine-resistant tumors.

The researchers traced this weakness to the mevalonate pathway, a cellular production line that produces precursors for cholesterol and other important biomolecules. Resistant cells had reduced its activity, leaving them vulnerable to further pharmacological disruption. Experiments showed that statins worked primarily by limiting materials needed for many proteins to function, rather than simply lowering cholesterol. Because these chemical networks are difficult to unravel, the team drew on UC Irvine professor David Fruman’s expertise studying the same pathway in leukemia treatment resistance.

Analyses of patient tumor data also linked lower levels of a key protein in this pathway to poorer outcomes after gemcitabine-based treatment. With further validation, that finding could help doctors choose treatments more precisely.

For first author Dr. Alica Katrin Michels, the collaboration continued after she returned from UC Irvine to her clinical duties as a gastroenterologist at University Hospital Ulm, Germany. “Countless Zoom calls across different time zones together with the enthusiasm and dedication of our entire author team helped bring the paper to completion,” Michels said. “I am grateful to everyone who contributed. This experience highlighted the value of teamwork, perseverance, and international collaboration.”

Because statins are already widely used, repurposing them could offer a practical route to expanding treatment options if clinical testing confirms their benefits. Study co-author Dr. Jennifer Valerin, a UCI Health oncologist and School of Medicine faculty member, described how the research is moving forward: “This paper deepens our understanding of resistance and has also created pre-clinical data that we have already used to bring this treatment to patients in the form of an investigator-initiated trial that is currently ongoing at the UC Irvine Chao Family Comprehensive Cancer Center.” The early-stage trial is evaluating pitavastatin alongside gemcitabine-based chemotherapy, with clinical studies needed to establish whether this approach safely improves outcomes for patients.

Promising new drugs targeting KRAS, a protein involved in pancreatic cancer growth, have attracted considerable attention recently. However, resistance to these drugs is nearly always observed so chemotherapies are still used, and interestingly, activation of RAS proteins is also highly dependent on the metabolic pathways blocked by statin treatment. Accordingly, understanding how tumors become resistant to treatment remains essential. Halbrook’s team expects to “continue to deploy metabolic targeting approaches like statin treatment that leverage our findings in a combination with the cutting-edge therapies that we are spearheading in clinical trials at the UCI Chao Family Comprehensive Cancer Center.” Continued public and philanthropic support for clinical trials and interdisciplinary research can help move these promising findings toward better options for patients and families.

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 bio.uci.edu.