Berriel Diaz Mauricio, Rohm Maria, Herzig Stephan
Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Department of Inner Medicine, Heidelberg University Hospital, Heidelberg, Germany.
Nat Metab. 2024 Dec;6(12):2222-2245. doi: 10.1038/s42255-024-01167-9. Epub 2024 Nov 22.
Cancer cachexia is a complex metabolic disorder marked by unintentional body weight loss or 'wasting' of body mass, driven by multiple aetiological factors operating at various levels. It is associated with many malignancies and significantly contributes to cancer-related morbidity and mortality. With emerging recognition of cancer as a systemic disease, there is increasing awareness that understanding and treatment of cancer cachexia may represent a crucial cornerstone for improved management of cancer. Here, we describe the metabolic changes contributing to body wasting in cachexia and explain how the entangled action of both tumour-derived and host-amplified processes induces these metabolic changes. We discuss energy homeostasis and possible ways that the presence of a tumour interferes with or hijacks physiological energy conservation pathways. In that context, we highlight the role played by metabolic cross-talk mechanisms in cachexia pathogenesis. Lastly, we elaborate on the challenges and opportunities in the treatment of this devastating paraneoplastic phenomenon that arise from the complex and multifaceted metabolic cross-talk mechanisms and provide a status on current and emerging therapeutic approaches.
癌症恶病质是一种复杂的代谢紊乱，其特征是体重意外减轻或身体质量“消耗”，由多个层面的多种病因驱动。它与许多恶性肿瘤相关，并显著导致癌症相关的发病率和死亡率。随着越来越认识到癌症是一种全身性疾病，人们越来越意识到，理解和治疗癌症恶病质可能是改善癌症管理的关键基石。在此，我们描述了导致恶病质中身体消耗的代谢变化，并解释了肿瘤衍生过程和宿主放大过程的相互作用如何诱导这些代谢变化。我们讨论了能量稳态以及肿瘤的存在干扰或劫持生理能量保存途径的可能方式。在此背景下，我们强调了代谢相互作用机制在恶病质发病机制中的作用。最后，我们阐述了由于复杂且多方面的代谢相互作用机制而在治疗这种毁灭性副肿瘤现象时所面临的挑战和机遇，并介绍了当前和新兴治疗方法的现状。
