Core Viewpoint - The article emphasizes the significant role of the dynamic interaction between tumor cells and the host in the pathogenesis of cancer cachexia, a syndrome affecting approximately 50%-80% of cancer patients, with varying incidence rates across different malignancies [2][4]. Group 1: Overview of Cancer Cachexia - Cancer cachexia is characterized by systemic inflammation, weight loss, and muscle and fat tissue atrophy, primarily due to increased energy expenditure, hypermetabolism, and anorexia [4]. - Clinical criteria for considering cancer cachexia risk include weight loss of ≥5% within six months, BMI <20 kg/m² with weight loss of ≥2%, and weight loss of ≥2% in sarcopenic patients [4]. - The syndrome significantly impacts patients' quality of life, exacerbates treatment-related toxicities, and increases mortality rates by 20%-30% [4]. Group 2: Mechanisms and Interactions - The review discusses the systemic metabolic syndrome involving multiple tissues and organs, including skeletal muscle, fat, and liver, and how tumors influence distant organs through neural, blood, and lymphatic networks [5][19]. - It posits that catabolic metabolism activation and anabolic metabolism suppression are key features in cancer cachexia, leading to inflammatory responses that disrupt energy homeostasis [5][23]. - The interplay between metabolic reprogramming and inflammatory responses creates a vicious cycle, with immune and stromal cells releasing inflammatory mediators that further disturb systemic metabolism [23][26]. Group 3: Recent Advances and Therapeutic Strategies - Recent studies highlight innovative therapeutic strategies aimed at alleviating cancer cachexia, including the approval of Anamorelin, a ghrelin receptor agonist, which has shown promise in increasing muscle mass and weight [25]. - Targeting specific inflammatory factors, such as GDF15 with Ponsegromab, has demonstrated potential in improving weight and activity levels in early clinical trials [25]. - Metabolic interventions, including supplementation with specific amino acid derivatives and ω-3 fatty acids, have been shown to alleviate symptoms of cancer cachexia [26]. Group 4: Future Research Directions - The complexity of cancer cachexia mechanisms necessitates further research to identify new therapeutic targets, integrating immunology and metabolomics approaches [26]. - The need for more comprehensive studies using optimal animal models to simulate cachexia states is emphasized to enhance understanding of the syndrome's progression [26].

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].