Scientists Identify Inhibition of a Specific Enzyme as a Promising Target to Treat Pancreatic Cancer

Researchers have identified a promising new target in the treatment of pancreatic cancer. A new studyopens in new tab/window in The American Journal of Pathologyopens in new tab/window, published by Elsevier, demonstrates that blocking complement factor B (CFB), a pivotal enzyme in the alternative complement pathway, halts cancer growth and alters the tumor microenvironment. The greatest tumor suppression was observed when CFB inhibition was combined with chemotherapy and immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat, in large part because of its highly immunosuppressive nature. Effective therapies are limited, and the five-year survival rate is below 15%.

The researchers of this study first examined the clinical significance of CFB in human PDAC tissues and found that high levels of the enzyme in the connective tissue surrounding the tumor were associated with poorer patient survival rates and more frequent hematogenous recurrence. They then investigated the effects of the selective CFB inhibitor iptacopan in pancreatic cancer cells and found that CFB blockade reduced cancer cell proliferation and promoted cellular senescence, accompanied by increased expression of p21, a protein that signals cancer cells to stop growing.

“Iptacopan is an already approved first-in-class oral CFB inhibitor that has shown clinical efficacy and safety in certain rare complement-mediated diseases,” explains lead investigator Shigetsugu Takano, MD, PhD, Department of General Surgery, Chiba University, Graduate School of Medicine, Japan. “In our previous research, we identified that CFB is upregulated during PDAC development. This led us to test the use of iptacopan in a mouse model of PDAC.”

Lead author Daren Zhou, MD, PhD, Department of General Surgery, Chiba University, Graduate School of Medicine, Japan, adds, “We demonstrated that iptacopan significantly suppressed tumor growth. Importantly, CFB blockade also altered the tumor immune microenvironment. We saw a decrease in regulatory T cells together with increased CD8+ T-cell infiltration, suggesting that CFB blockade was doing more than directly affecting tumor cells; it was also reshaping the immune context of the tumor. This finding led us to explore combination therapy with immune checkpoint blockades, where we observed additional antitumor activity.”

Because pancreatic cancer creates an exceptionally immunosuppressive environment, targeting the tumor cells directly via immunotherapy has had limited success. This study shows that CFB may be one of the mechanisms helping to maintain that defensive environment. CFB inhibition targets both the cancer cells and their surroundings.

Dr. Takano concludes, “Our findings support iptacopan’s potential as a combination therapy with chemotherapy and immunotherapy, although further preclinical and clinical studies are needed. We hope these findings will contribute to developing new, more effective treatments for pancreatic cancer.”

Notes for editors

The article is “Complement Factor B Blockade by Iptacopan Drives Antitumor Complement-Based Immunomodulation in Pancreatic Cancer Microenvironment,” by Daren Zhou, Shigetsugu Takano, Kazuyuki Sogawa, Ryo Moriyasu, Tsukasa Takayashiki, Daisuke Suzuki, Nozomu Sakai, and Masayuki Ohtsuka (https://doi.org/10.1016/j.ajpath.2026.08.005opens in new tab/window). It appears online ahead of The American Journal of Pathology, volume 196, issue 12 (December 2026), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(26)00257-9/fulltextopens in new tab/window.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 406 1313 or [email protected]opens in new tab/window to request a PDF of the article or more information. To reach the study’s authors, contact Shigetsugu Takano, MD, PhD, Department of General Surgery, Chiba University Graduate School of Medicine, at [email protected]opens in new tab/window.

This study was conducted as a collaborative research project involving Chiba University, Denka Company Limited, and Azabu University. The authors would also like to acknowledge the research support from Denka Company Limited and the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research.

About The American Journal of Pathology

The American Journal of Pathologyopens in new tab/window, official journal of the American Society for Investigative Pathologyopens in new tab/window, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. ajp.amjpathol.orgopens in new tab/window

About Elsevier

Elsevier is a global leader in advanced information and decision support. For over a century, we have been helping advance science and healthcare to advance human progress. We support academic and corporate research communities, doctors, nurses, future healthcare professionals, and educators across 170 countries in their vital work. We help impact makers achieve better outcomes with research and clinical-grade solutions built on the world’s leading evidence-based scientific and medical content, precision AI, and expert human assessment. We champion inclusion and sustainability, working with the communities that we serve. The Elsevier Foundationopens in new tab/window supports research and health partnerships around the world.

Elsevier is part of RELXopens in new tab/window, a global provider of information-based analytics and decision tools for professional and business customers. For more information, visit www.elsevier.com and follow us on social media @elsevierconnect.