A staggering 50-80% of cancer patients experience cachexia, a debilitating syndrome marked by unintentional weight loss, and it’s far more than just “muscle wasting.” Losing 10% of body weight within six months—a goal some actively pursue—becomes a source of frustration for those battling cancer, as they desperately *want* to gain weight but find themselves unable to.
The Metabolic Mystery Behind Cancer Cachexia
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Understanding how cancer rewires the body’s metabolism could unlock new treatments.
- Cachexia isn’t simply about losing appetite; it’s a complex metabolic shift affecting multiple organs.
- Researchers have identified a “One Carbon Cycle” activation as a universal signature of cachexia, regardless of cancer type.
- Targeting this metabolic process could potentially prevent muscle atrophy and improve quality of life for cancer patients.
- Currently, there are no approved drugs specifically for cancer cachexia, highlighting the need for new therapeutic strategies.
For years, research focused on muscle loss as the most functionally relevant aspect of cachexia—understandably, as it directly impacts a patient’s ability to perform daily tasks. However, a new study shifts the focus, examining the changes occurring across the *entire* body’s metabolism. “Until now, it was completely unclear how the metabolic reactions of different organs work together to drive cancer-related weight loss,” explains Dr. Maria Rohm, group leader at the Institute for Diabetes and Cancer. “We wanted to better understand the nature of weight loss through an integrated analysis of different organs.”
A Universal Metabolic Signature Emerges
By analyzing the metabolome and transcriptome in eight different organs of tumor-bearing mice—both with and without cachexia—researchers established metabolic signatures characteristic of cancer-mediated weight loss. This high-throughput analysis revealed a cachexia-specific metabolic signature and identified genetic markers offering insights into the progression of these metabolic changes.
The study pinpointed increased activation of the “One Carbon Cycle” – a crucial biochemical process for synthesizing nucleotides, amino acids, and supporting cell regeneration – across all organs. Products of this cycle, such as sarcosine and dimethylglycine, show promise as potential biomarkers for early cachexia detection. Interestingly, hyperactivation of the “One Carbon Cycle” in muscle correlated with increased glucose metabolism and muscle atrophy, and initial experiments suggest inhibiting this process could prevent muscle breakdown.
“The fact that all organs react metabolically to cachexia in the same way was a surprise to us,” says Rohm. “The organs lose their individual metabolic signature and instead switch to this coordinated metabolic process.” Comparative analyses across eight different mouse tumor models (lung, colon, and pancreatic cancer) confirmed that this “One Carbon” signature is a universal indicator of cachexia, irrespective of the cancer’s origin.
Can We Normalize Metabolism to Fight Cachexia?
Currently, there are no approved drugs for cancer cachexia in Germany. However, research is underway to develop approaches to combat cancer-related loss of appetite. This new study offers the first evidence suggesting that normalizing metabolism itself could be a viable strategy. Initial cell culture experiments demonstrate that interventions targeting the “One Carbon Cycle” can yield positive effects.
Future research will determine whether a systemic approach to the “One Carbon Cycle” is most effective, or if targeted therapies focusing on individual organs—like muscle—are necessary. This is a key focus of the DFG “HyperMet” research group, which aims to normalize both appetite and metabolic processes in cachexia, ultimately improving patient quality of life and cancer treatment outcomes.
Morigny et al., 2026: Multi-omics profiling of cachexia-target tissues reveals a spatio-temporal coordinated response to cancer. Nature Metabolism. DOI: 10.1038/s42255-025-01434-3
Dr. Maria Rohm is a group leader at the Institute for Diabetes and Cancer and a researcher at the German Center for Diabetes Research, the German Center for Cardiovascular Research, and the Heidelberg University Hospital.
Dr. Ondřej Kuda is Director of the Institute of Physiology at the Czech Academy of Sciences in Prague.
Dr. Pauline Morigny is a senior researcher at the Institute for Diabetes and Cancer and at the University Hospital Heidelberg.
