Metabolic Switch Against Lung Cancer
Researchers at Justus Liebig University Discover New Therapeutic Approach
No. 76 • 8 June 2026
(deutsche Version hier)
An international research team, led by Justus Liebig University Giessen (JLU), the Institute for Lung Health (ILH) in Giessen, and the Max Planck Institute for Heart and Lung Research in Bad Nauheim, has identified a promising mechanism for combating lung cancer. The researchers discovered that a specific endogenous metabolic process can induce the immune system to directly attack tumor cells and stop their growth. This opens new avenues for targeted therapies. The results have been published in the journal “Cell Metabolism”.
Lung cancer is one of the most common cancers worldwide, with a particularly high mortality rate. A decisive factor in the progression of the disease is the tumor microenvironment—the surroundings in which the tumor grows. Here, certain immune cells, known as macrophages (“scavenger cells”), play a dual role: they can either fight the tumor or even support it, thereby promoting cancer growth.
The "Metabolic Switch": Itaconate
The research team led by Prof. Dr. Rajkumar Savai, Professor of Lung Microenvironmental Niche in Cancerogenesis at JLU, investigated how controlling cellular metabolism can reprogram these immune cells. At the center of this is the molecule itaconate. The researchers found that there is a natural deficiency of itaconate in lung cancer regions. This deficiency causes the macrophages to switch to a pro-tumoral form that supports the cancer. However, when the team artificially increased the itaconate concentration, something decisive happened: the macrophages switched to an anti-tumoral state. They became active defenders that slowed tumor growth, as the researchers investigated in mouse models and human tissue samples.
Direct Influence on Cancer Cells
Itaconate has another positive effect: the molecule does not act only indirectly via the immune system. The researchers were able to show that a variant called octyl-itaconate also attacks the cancer cells directly. This substance blocks an important enzyme (G6PD) that is essential for the metabolism of the cancer cells. Without this enzyme, the tumor cells lack the necessary “fuel” for their rapid multiplication, which stops the growth.
A New Approach for Cancer Therapy
“Our results show that by specifically influencing metabolism, we can both strengthen the immune system and directly weaken the cancer cells,” says Prof. Savai, last author of the study. “It is particularly significant that the effect could also be demonstrated in human lung tissue sections, which underlines the relevance for clinical application.” The study thus provides an important basis for the development of new drugs aimed at starving the cancer cells' metabolism while simultaneously activating the body's own defenses.
The work was produced in a cooperation between JLU, the Institute for Lung Health, the Max Planck Institute for Heart and Lung Research in Bad Nauheim, the German Center for Lung Research (DZL), and other international partners. The research was funded, among others, by the German Research Foundation (DFG), the State of Hesse (LOEWE Schwerpunkt iCANx), the European Research Council (ERC), and the EU Framework Programme for Research and Innovation Horizon Europe (Project COMBAT).
Publication
Siavash Mansouri, Golnaz Hesami, Anoop Ambikan, Annika Karger, Stephan Klatt, Ujjwal Neogi, Konda Babu Kurakula, Blerina Aliraj, Anne Miller, Boryana Petrova, Miloslav Sanda, Evelyn Sirait-Fischer, Stefan Guenther, Carsten Kuenne, Clemens Ruppert, Ibrahim Alkoudmani, Stefan Gattenlöhner, Sven Zukunft, Ingrid Fleming, Arvand Haschemi, Thorsten Stiewe, Friedrich Grimminger, Martin Reck, Andreas Weigert, Werner Seeger, Soni Savai Pullamsetti, Rajkumar Savai: IRG1/itaconate rewires macrophage and lung tumor metabolism through G6PD Inhibition. Cell Metabolism, online veröffentlicht am 3. Juni 2026
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00190-7
Contact
Rajkumar Savai
Professor and Chair for Lung Microenvironmental Niche in Cancerogenesis
Institute for Lung Health (ILH)
Justus Liebig University Giessen, Germany
Phone: 0049 641 99-42351
E-mail: savai.rajkumar
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