A research team from the University of Graz has pinpointed interleukin-6 (IL-6) as the central trigger for cancer cachexia, the severe, life-threatening weight loss that claims the lives of about one in five cancer patients. The breakthrough, stemming from an unexpected observation in cell cultures, has paved the way for a compound that halted tissue breakdown in animal models. A clinical trial is now underway in the United States.
Cachexia affects roughly half of all cancer patients and operates as an independent condition: despite adequate calorie intake, the body aggressively degrades fat, muscle, and functional tissue—most dramatically in pancreatic and gastric cancers. Even forced feeding via infusion fails, as tumors emit signals that trick the body into a starvation response, depleting its reserves.
The Austrian Science Fund (FWF)-backed project (2022–2026, €256,000) sought the molecular culprits distinguishing cachexia-inducing tumors from benign ones. A pivotal moment came when a previously non-cachectic cancer cell line spontaneously mutated to trigger the syndrome, enabling direct comparison. This revealed IL-6, an immune signaling molecule, as the decisive factor: only cachexia-causing cells produced it in abundance. The cytokine forms a blood-borne complex with its receptor, docking onto muscle and fat cells to initiate their destruction. Removing IL-6 from cells or circulation completely prevented cachexia.
Published in 2023 in the Journal of Cachexia, Sarcopenia and Muscle, the findings include a shared cell model for global research.
Repurposed Painkiller Shows Promise
Collaborating with a Chinese partner, the team identified R-ketorolac—the mirror-image form of the common postoperative analgesic S-ketorolac—as a therapeutic candidate. In mice, it lowered IL-6 levels, boosted T-lymphocytes, and slowed weight loss even during chemotherapy, significantly improving survival. Results appeared in 2024 in the same journal.
The compound is currently in a Phase I trial at Cedars-Sinai Medical Center in Los Angeles for patients with advanced pancreatic cancer.
Collaborations and Future Directions
Working with a Graz colleague, the team developed a magnetic resonance spectroscopy method to monitor tumor energy status in living organisms, detailed in a 2024 NMR in Biomedicine paper. Joint lipid metabolism analysis with Hungarian partners in Szeged showed that lipid balance affects tumor growth but not cachexia induction.
Future efforts will focus on the tumor microenvironment and immune cell profiling to enable immunotherapy. Chemotherapy often proves fatal for cachectic patients; the ultimate goal is to stabilize weight long enough to treat the underlying cancer effectively.
Lead Researcher: Martina Schweiger, Professor of Biochemistry and Molecular Biology, Co-Director of BioTechMed-Graz, specializes in fat metabolism in health and disease, from obesity to cachexia.
Source: Scilog – Science Magazine of the Austrian Science Fund (FWF)
Sources:
- https://scilog.fwf.ac.at/biologie-medizin/den-toedlichen-gewichtsverlust-bei-krebs-stoppen
- Interleukin-6 initiates muscle- and adipose tissue wasting in a novel C57BL/6 model of cancer-associated cachexia. Journal of Cachexia, Sarcopenia and Muscle, 2023. DOI: 10.1002/jcsm.13168
- R-ketorolac ameliorates cancer-associated cachexia and prolongs survival of tumour-bearing mice. Journal of Cachexia, Sarcopenia and Muscle, 2024. DOI: 10.1002/jcsm.13456
- Robust dual-angle T1 measurement in magnetization transfer spectroscopy by time-optimal control. NMR in Biomedicine, 2024. DOI: 10.1002/nbm.5201
