Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
Adv Exp Med Biol. 2017;1026:233-249. doi: 10.1007/978-981-10-6020-5_11.
Wasting of adipose tissue and skeletal muscle is a hallmark of metastatic cancer and a major cause of death. Like patients with cachexia caused by other chronic infections or inflammatory diseases, the cancer subject manifests both malnutrition and metabolic stress. Both carbohydrate utilization and amino acid incorporation are decreased in the muscles of cancer cachexia patients. Cancer cells affect host metabolism in two ways: (a) their own metabolism of nutrients into other metabolites and (b) circulating factors they secrete or induce the host to secrete. Accelerated glycolysis and lactate production, i.e., the Warburg effect and the resultant increase in Cori cycle activity, are the most widely discussed metabolic effects. Meanwhile, although a large number of pro-cachexia circulating factors have been found, such as TNFa, IL-6, myostatin, and PTHrp, none have been shown to be a dominant factor that can be targeted singly to treat cancer cachexia in humans. It is possible that given the complex multifactorial nature of the cachexia secretome, and the personalized differences between cancer patients, targeting any single circulating factor would always be insufficient to treat cachexia for all patients. Here we review the metabolic changes that occur in response to tumor growth and tumor-secreted factors during cachexia.
脂肪组织和骨骼肌的消耗是转移性癌症的标志，也是死亡的主要原因。与由其他慢性感染或炎症性疾病引起的恶病质患者一样，癌症患者既有营养不良又有代谢应激。癌症恶病质患者的肌肉中碳水化合物的利用和氨基酸的掺入都减少了。癌细胞通过两种方式影响宿主代谢：（a）自身将营养物质代谢为其他代谢物，（b）它们分泌或诱导宿主分泌的循环因子。加速糖酵解和乳酸生成，即沃伯格效应，以及由此导致的科里循环活性增加，是最广泛讨论的代谢效应。同时，尽管已经发现了大量的促恶病质循环因子，如 TNFa、IL-6、肌肉生长抑制素和 PTHrp，但没有一种被证明是可以单独针对人类恶病质的优势因子。可能是由于恶病质分泌组的复杂多因素性质，以及癌症患者之间的个体差异，针对任何单一的循环因子，对于所有患者的治疗恶病质总是不够的。在这里，我们回顾了在恶病质期间肿瘤生长和肿瘤分泌因子引起的代谢变化。
