Penna Fabio, Ballarò Riccardo, Beltrà Marc, De Lucia Serena, García Castillo Lorena, Costelli Paola
Department of Clinical and Biological Sciences, Interuniversity Institute of Myology, University of Turin, Turin, Italy.
Front Physiol. 2019 Feb 18;10:41. doi: 10.3389/fphys.2019.00041. eCollection 2019.
The management of cancer patients is frequently complicated by the occurrence of cachexia. This is a complex syndrome that markedly impacts on quality of life as well as on tolerance and response to anticancer treatments. Loss of body weight, wasting of both adipose tissue and skeletal muscle and reduced survival rates are among the main features of cachexia. Skeletal muscle wasting has been shown to depend, mainly at least, on the induction of protein degradation rates above physiological levels. Such hypercatabolic pattern is driven by overactivation of different intracellular proteolytic systems, among which those dependent on ubiquitin-proteasome and autophagy. Selective rather than bulk degradation of altered proteins and organelles was also proposed to occur. Within the picture described above, the muscle is frequently considered a sort of by-stander tissue where external stimuli, directly or indirectly, can poise protein metabolism toward a catabolic setting. By contrast, several observations suggest that the muscle reacts to the wasting drive imposed by cancer growth by activating different compensatory strategies that include anabolic capacity, the activation of autophagy and myogenesis. Even if muscle response is eventually ill-fated, its occurrence supports the idea that in the presence of appropriate treatments the development of cancer-induced wasting might not be an ineluctable event in tumor hosts.
癌症患者的管理常常因恶病质的出现而变得复杂。这是一种复杂的综合征，对生活质量以及对抗癌治疗的耐受性和反应都有显著影响。体重减轻、脂肪组织和骨骼肌消瘦以及生存率降低是恶病质的主要特征。骨骼肌消瘦已被证明至少主要取决于蛋白质降解率高于生理水平的诱导。这种高分解代谢模式是由不同细胞内蛋白水解系统的过度激活驱动的，其中那些依赖泛素 - 蛋白酶体和自噬的系统。还提出了对改变的蛋白质和细胞器进行选择性而非大量降解。在上述情况中，肌肉常被视为一种旁观者组织，外部刺激可直接或间接使蛋白质代谢倾向于分解代谢状态。相比之下，一些观察结果表明，肌肉通过激活不同的补偿策略来应对癌症生长所施加的消瘦驱动，这些策略包括合成代谢能力、自噬激活和肌生成。即使肌肉反应最终命运不佳，其出现也支持了这样一种观点，即在存在适当治疗的情况下，癌症诱导的消瘦在肿瘤宿主中可能并非不可避免的事件。
