Department of Nutrition, Food, and Exercise Sciences, The Florida State University, 432 Sandels Building, Tallahassee, FL 32306-1493, USA.
Anticancer Agents Med Chem. 2013 Oct;13(8):1188-96. doi: 10.2174/18715206113139990321.
Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass represents an important objective in the cancer patient trajectory not only because it relates to one's capacity to perform activities of daily living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard, research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches, administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by highlighting the cellular and molecular aspects of HMB function.
癌症恶病质是一种危及生命的疾病，其特征是体重不自主下降和骨骼肌消耗。除了与不良预后和生存时间减少相关外，恶病质患者还表现出严重的身体功能丧失，这影响了他们进行日常基本活动的能力。因此，他们会失去独立性，并大大降低生活质量。尽管这是癌症患者的一个主要未满足的医疗需求，但几乎没有治疗选择。保持肌肉质量是癌症患者治疗轨迹中的一个重要目标，不仅因为它与一个人进行日常活动的能力有关，而且因为肌肉的保存可能是在肿瘤携带状态下生存的一个关键决定因素。在这方面，研究已经针对确定有效的肌肉保护对策。在营养方法方面，亮氨酸代谢产物β-羟基-β-甲基丁酸（HMB）的给药可能是针对癌症恶病质的多模式治疗的一个可行组成部分。有证据表明，HMB 治疗可促进再生事件（即肌生成程序）、抑制蛋白质降解，并激活蛋白质合成和骨骼肌生长之前的信号通路。因此，HMB 可以想象作用于驱动癌症恶病质的关键调节事件，从而有利于肌肉生长/保存。在这篇综述中，我们通过强调 HMB 功能的细胞和分子方面，以一种机制的方法来证明 HMB 供应作为癌症恶病质的一种可能治疗策略的使用。
