Core Viewpoint - Cancer cachexia significantly alters the metabolism of patients, leading to involuntary weight loss and increased mortality, with no FDA-approved treatments available to fully reverse the condition [2][3][6]. Group 1: Cancer Cachexia Overview - 50%-80% of cancer patients experience cancer cachexia, resulting in functional decline, decreased quality of life, increased chemotherapy toxicity, and higher mortality rates [3]. - Cancer cachexia accounts for at least 20% of cancer-related deaths, highlighting the urgency for effective treatments [3]. Group 2: Research Findings - A study published in Cell identified the liver as a previously overlooked driver of cancer cachexia, revealing that the disruption of the biological clock gene REV-ERBα in the liver promotes the release of hepatokines that enhance catabolism [4][5]. - Reactivating REV-ERBα expression or inhibiting specific hepatokines (LBP, ITIH3, IGFBP1) significantly improved weight loss in mouse models of cancer cachexia [5][11]. Group 3: Mechanisms of Action - The study demonstrated that the liver undergoes metabolic reprogramming in cancer cachexia, with the biological clock gene REV-ERBα becoming inactive, leading to increased release of catabolic hepatokines [10][11]. - In cancer cachexia patients, levels of LBP, ITIH3, and IGFBP1 were significantly elevated compared to weight-stable cancer patients, indicating their role in promoting tissue wasting [12][15]. Group 4: Implications for Treatment - The findings suggest that the liver actively contributes to the progression of cancer cachexia rather than being a passive responder, providing new biomarkers and therapeutic targets for better diagnosis and treatment interventions [16].