Liver's Role in Cancer Cachexia: New Insights from Recent Study

A groundbreaking study published in the journal Cell on July 21, 2025, reveals that the liver plays a significant role in cancer cachexia, a debilitating syndrome characterized by severe muscle and fat tissue loss in cancer patients. This research, conducted by a team from Helmholtz Munich in collaboration with Heidelberg University Hospital and the Technical University of Munich, highlights how the liver responds to tumors in other organs, leading to systemic signaling that exacerbates tissue wasting.

Cachexia affects approximately half of all cancer patients and is linked to increased mortality, therapy resistance, and complications during treatment. According to Dr. Mauricio Berriel Diaz, the study's lead researcher and a prominent figure at Helmholtz Munich, "For the first time, we were able to show that the liver is not merely a passive responder to cachexia, but actively contributes to the progression of the disease."

The researchers discovered that the metabolism of the liver undergoes significant reprogramming in cachexia. One specific gene, REV-ERBα, which is responsible for regulating liver activity, becomes nonfunctional. Dr. Doris Kaltenecker, co-first author and researcher at the Institute for Diabetes and Cancer at Helmholtz Munich, noted that reactivating this gene in affected mice significantly reduced body mass loss.

The study identified three hepatokines—LBP, ITIH3, and IGFBP1—that play a crucial role in promoting the catabolic processes associated with cachexia. Elevated levels of these proteins were found in the blood of cachectic patients, suggesting their potential as biomarkers for cachexia risk and targets for new therapies. Dr. Kaltenecker further explained, "When the clock gene is inactive, the liver releases increased levels of factors that promote disease progression."

As the research progresses, the data collected will be made available to the scientific community, paving the way for further investigations into effective diagnostic and therapeutic strategies. Prof. Stephan Herzig, Director of the Helmholtz Diabetes Center, emphasized the urgent need for new approaches, stating, "Given that there is currently no approved treatment for cachexia, we urgently need new approaches."

This study not only advances our understanding of cancer cachexia but also underscores the importance of systemic organ interactions in disease progression. As researchers continue to explore the links between the liver and cachexia, there is hope for developing targeted therapies that could transform the management of this challenging syndrome for cancer patients. The implications of these findings may extend beyond cachexia, potentially influencing approaches to other metabolic disorders associated with cancer.

In conclusion, the identification of the liver's active role in cachexia opens new avenues for research and therapeutic interventions, highlighting the need for a multidisciplinary approach to tackle the complexities of cancer and its associated syndromes.