{"id":122508,"date":"2025-05-30T01:58:00","date_gmt":"2025-05-30T06:58:00","guid":{"rendered":"https:\/\/www.unmc.edu\/newsroom\/?p=122508"},"modified":"2025-09-30T14:25:13","modified_gmt":"2025-09-30T19:25:13","slug":"unmc-researchers-find-promising-target-for-lung-cancer-treatment","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/newsroom\/2025\/05\/30\/unmc-researchers-find-promising-target-for-lung-cancer-treatment\/","title":{"rendered":"UNMC researchers find promising target for lung cancer treatment"},"content":{"rendered":"
\n

A UNMC research team, including postdoctoral research associate Muthamil Iniyan Appadurai, PhD, and assistant professor Imayavaramban Lakshmanan, PhD, has identified a novel mechanism that may help explain not only how lung cancer evades the immune system but also uncovered a potential new therapeutic target.<\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

Their findings, recently published in the Journal of Clinical Investigation<\/a>, focus on an enzyme called ST6GalNAc-I, a sialyltransferase that conjugates sialic acid to proteins.<\/p>\n\n\n\n

\u201cThis enzyme was highly overexpressed in both mouse lung tumor models and in human lung cancer samples, but it showed minimal expression in normal lung tissue,\u201d said Dr. Lakshmanan, assistant professor in the UNMC Department of Biochemistry and Molecular Biology and a member of the Fred & Pamela Buffett Cancer Center. \u201cThat contrast made it a strong candidate for further investigation.\u201d<\/p>\n\n\n\n

Drawing on gene expression datasets and in preclinical models, the team identified two primary mechanisms by which ST6GalNAc-I promotes lung cancer progression: by facilitating tumor cells escape from the immune system, and by fueling the formation of new blood vessels, a process known as angiogenesis.<\/p>\n\n\n\n

By adding a terminal sugar molecule, sialic acid, to glycoproteins such as mucin 5AC and Nectin2, it creates \u201ca kind of camouflage,\u201d Dr. Lakshmanan said. \u201cThese sugar-coated proteins interfere with immune surveillance, allowing tumors to grow unchecked.\u201d<\/p>\n\n\n\n

Dr. Lakshmanan refers to this interaction as a \u201cglyco-immune checkpoint,\u201d a novel concept inspired by existing immune checkpoint therapies.<\/p>\n\n\n\n

In addition to immune evasion, the enzyme was found to play a role in nourishing tumor growth. \u201cWe observed a significant reduction in tumor progression and cell migration when we knocked down this enzyme in our lung cancer models,\u201d Dr. Lakshmanan said. \u201cThat was a major finding.\u201d<\/p>\n\n\n\n

The group is now partnering with a biotech company in the Netherlands to test a drug that inhibits the sialic acid glycosylation driven by ST6GalNAc-I. \u201cWe\u2019re exploring combination strategies using this drug alongside immunotherapy,\u201d Dr. Lakshmanan said. \u201cOur goal is to enhance the efficacy of existing treatments.\u201d<\/p>\n\n\n

\n
\"\"
Postdoctoral research associate Muthamil Iniyan Appadurai, PhD, and assistant professor Imayavaramban Lakshmanan, PhD<\/figcaption><\/figure>\n<\/div>\n\n\n

The research was a multidisciplinary effort involving key collaborators, including Surinder Batra, PhD, Hartmann Chair in the UNMC Department of Biochemistry and Molecular Biology and director of translational research at the Fred & Pamela Buffett Cancer Center, and Apar Kishor Ganti, MD, associate director for clinical research at the Fred & Pamela Buffett Cancer Center. \u201cBeing able to work so closely with both clinicians and basic scientists has been invaluable,\u201d Dr. Lakshmanan said.<\/p>\n\n\n\n

The project began with RNA sequencing studies that highlighted ST6GalNAc-I as one of the most highly expressed genes in lung cancer tissue. Building on that discovery, Dr. Lakshmanan received a National Institutes of Health R21 grant. The team is now working to develop neutralizing antibodies that target ST6GalNAc-I modified glycoproteins.<\/p>\n\n\n\n

If preclinical models continue to show promise, the therapy could move into clinical trials with support from Dr. Ganti\u2019s clinical oncology team.<\/p>\n\n\n\n

For Dr. Appadurai, UNMC\u2019s collaborative environment has helped him grow as a researcher. \u201cWe\u2019re given access to cutting-edge tools and mentorship,\u201d he said. \u201cIt\u2019s a great place to grow and contribute to patient-centered science.\u201d<\/p>\n\n\n\n

He expressed deep gratitude for his mentors and the collaborative environment at UNMC, noting the strong integration between basic science and clinical teams. Looking ahead, Dr. Appadurai said he plans to become an independent researcher, where he can continue contributing to cancer research and the development of new treatments.<\/p>\n<\/div><\/div>","protected":false},"excerpt":{"rendered":"

The multidisciplinary team recently published their findings in the Journal of Clinical 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