编辑丨王多鱼 排版丨水成文 癌症恶病质 （ C ancer Cachexia ） 是一种由肿瘤特异性生物学过程驱动的复杂多器官综合征，会导致全 身代谢功能障碍。其特征为骨骼肌和脂肪组织逐渐消耗导致的进行性体重减轻，通常伴有食欲减退，最终 导致生活质量下降和预后不良。恶病质在胰腺癌、肺癌、食管癌和胃癌等癌症中尤为常见，这些癌症加起 来占全球癌症相关死亡人数的近一半。 迄今为止，尚无获得美国 FDA 批准的有效逆转癌症恶病质的疗法，这凸显了这一关键的未满足需求。新出 现的证据表明，肿瘤与多个器官系统之间的相互作用在驱动恶病质方面起着关键作用，这突显了肿瘤微环 境的重要性。阐明这些全身性相互作用的机制对于开发有效的治疗方法和扩大治疗选择至关重要。 2 026 年 2 月 1 2 日，俄克拉荷马大学医学院 李敏 教授团队等在 Cancer Cell 期刊发表了题为： Tumor-immune-neural circuit disrupts energy homeostasis in cancer cachexia 的研究论文。 该研究首次系统揭示了由 肿瘤 、 免疫系统 和 神经系统 共同构成的病理环路，并证实该环路 ...

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].