How Fatty Liver Disease Helps Colorectal Cancer Spread
Cedars-Sinai Investigators Identify Possible Ways to Reduce Cancer Growth and Make Immunotherapy More Effective
Patients with a condition called steatotic liver disease, also known as fatty liver disease, are at increased risk for developing colorectal cancer—and for that cancer to metastasize (spread) to the liver. A preclinical study from Cedars-Sinai investigators suggests a way to stop the growth of liver metastasis in these patients and to make immunotherapy treatment more effective in shrinking their tumors. The findings were published in the peer-reviewed Journal of Clinical Investigation.
“Obesity and fatty liver are known risk factors for colorectal cancer and for colorectal cancer liver metastasis,” said Ekihiro Seki, MD, PhD, professor of Medicine and Biomedical Sciences at Cedars-Sinai and senior author of the study. “We found that accumulation in the liver of a substance called hyaluronic acid, which causes fibrosis and is more common in patients with fatty liver, activates cells that help cancer spread. It also suppresses immune cells, making immunotherapy treatments less effective.”
By inhibiting hyaluronic acid production in laboratory mice with fatty liver disease and liver metastasis, investigators improved the effectiveness of immunotherapy. The study confirms that patients with fatty liver disease and liver metastasis require different treatment strategies than patients with an otherwise healthy liver, Seki said.
Additional Cedars-Sinai authors include Yoon Mee Yang, Jieun Kim, Zhijun Wang, Jina Kim, So Yeon Kim, Takashi Tsuchiya, Michitaka Matsuda, Vijay Pandyarajan, Stephen J. Pandol, Michael S. Lewis, Alexandra Gangi, Paul W. Noble, Dianhua Jiang, Akil Merchant, Edwin M. Posadas, Neil A. Bhowmick, Shelly C. Lu, Sungyong You and Alexander M. Xu.
Additional authors include Gyu Jeong Cho, Jee Hyung Lee, and Sun Myoung Kim.
Funding: This work is supported by the National Institutes of Health (P01CA233452 to E.S., N.B., S.P., E.P., S.Y.Y., and S.C.L.; R21AA025841 to E.S. and S.C.L.; R01DK085252 and R01DK138591 to E.S.), NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI (UL1TR001881 to A.M.X.), the Center for Integrated Research in Cancer and Lifestyle Award, and a Project Acceleration Award by the Cedars-Sinai Cancer Center at Cedars-Sinai Medical Center (to E.S. and S.P.), grants from the National Research Foundation of Korea (RS-2023-00301850, RS-2023-00210489, and RS-2024-00441114 to Y.M.Y.), and American Liver Foundation Postdoctoral Fellowship (to J.K.).
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