Cheng Chen, Liu Ying, Chen Yuchen, Li Jiaying, Xu Weiqi, Perrimon Norbert, Song Wei
Department of Geriatrics, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei, China.
Adv Exp Med Biol. 2025;1482:83-100. doi: 10.1007/978-3-031-97035-1_5.
Late-stage cancer patients often exhibit cachexia, a wasting syndrome characterized by the loss of muscle and adipose tissues. However, the extent to which these wasting effects directly contribute to mortality remains unclear. Drosophila, a well-conserved model organism, has been instrumental in demonstrating systemic energy wasting and mortality in the context of tumors, similar to mice and humans. Research in Drosophila has elucidated the underlying mechanisms by which tumor-associated secreted proteins cause muscle atrophy and lipid loss, ultimately leading to energy wasting. Nevertheless, emerging evidence in both Drosophila and mammals challenges the notion that blocking energy loss in muscle or fat is sufficient to improve tumor-associated mortality, suggesting the existence of additional pathogenic factors in cancer cachexia. This raises two critical questions: how do tumors disrupt the physiological functions of other organs besides muscle and fat, and to what extent do these organ dysfunctions contribute to tumor-induced mortality? In this chapter, we summarize current knowledge regarding how fly tumors interact with host organs or tissues through the production of cachectic secreted proteins, and how they influence disease progression. We also discuss the power of Drosophila models in uncovering the mechanisms and principles of tumor-induced wasting and mortality and exploring therapeutic opportunities using various leading technologies.
晚期癌症患者常表现出恶病质，这是一种以肌肉和脂肪组织丢失为特征的消耗综合征。然而，这些消耗效应直接导致死亡率的程度仍不清楚。果蝇是一种保存良好的模式生物，在证明肿瘤情况下的全身能量消耗和死亡率方面发挥了重要作用，类似于小鼠和人类。对果蝇的研究阐明了肿瘤相关分泌蛋白导致肌肉萎缩和脂质流失，最终导致能量消耗的潜在机制。尽管如此，果蝇和哺乳动物中出现的新证据对阻断肌肉或脂肪中的能量流失足以改善肿瘤相关死亡率这一观点提出了挑战，这表明癌症恶病质中存在其他致病因素。这就引出了两个关键问题：肿瘤如何破坏除肌肉和脂肪之外的其他器官的生理功能，以及这些器官功能障碍在多大程度上导致肿瘤诱导的死亡？在本章中，我们总结了关于果蝇肿瘤如何通过产生恶病质分泌蛋白与宿主器官或组织相互作用，以及它们如何影响疾病进展的现有知识。我们还讨论了果蝇模型在揭示肿瘤诱导的消耗和死亡的机制和原理以及利用各种前沿技术探索治疗机会方面的作用。
