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有前景的癌症恶病质药物发现模型。

Promising models for cancer-induced cachexia drug discovery.

机构信息

Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Germany and German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany.

Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Expert Opin Drug Discov. 2020 May;15(5):627-637. doi: 10.1080/17460441.2020.1724954. Epub 2020 Feb 13.

Abstract

: Cachexia is a frequent, multifactorial syndrome associated with cancer afflicting patients' quality of life, their ability to tolerate anti-neoplastic therapies and the therapies efficacy, as well as survival. Currently, there are no approved cancer cachexia treatments other than those for the treatment of the underlying cancer. Cancer cachexia (CC) is poorly understood and hence makes clinical trial design difficult at best. This underlines the importance of well-characterized animal models to further elucidate the pathophysiology of CC and drug discovery/development.: This review gives an overview of the available animal models and their value and limitations in translational studies.: Using more than one CC model to test research questions or novel compounds/treatment strategies is strongly advisable. The main reason is that models have unique signaling modalities driving cachexia that may only relate to subgroups of cancer patients. Human xenograph CC models require the use of mice with a compromised immune system, limiting their value for translational experiments. It may prove beneficial to include standard care chemotherapy in the experimental design, as many chemotherapeutic agents can induce cachexia themselves and alter the metabolic and signaling derangements of CC and thus the response to new therapeutic strategies.

摘要

恶病质是一种常见的多因素综合征,与癌症有关,影响患者的生活质量、对抗肿瘤治疗的耐受性和治疗效果以及生存。目前,除了治疗基础癌症的治疗方法外,没有批准用于治疗恶病质的方法。恶病质(CC)的理解很差,因此使得临床试验设计变得非常困难。这突出了特征明确的动物模型的重要性,以进一步阐明 CC 的病理生理学和药物发现/开发。本文综述了现有的动物模型及其在转化研究中的价值和局限性。强烈建议使用多种 CC 模型来测试研究问题或新型化合物/治疗策略。主要原因是模型具有独特的信号方式驱动恶病质,这可能仅与癌症患者的亚组有关。人源异种移植 CC 模型需要使用免疫系统受损的小鼠,这限制了它们在转化实验中的价值。在实验设计中纳入标准的化疗可能会有所帮助,因为许多化疗药物本身可以诱导恶病质,并改变 CC 的代谢和信号紊乱,从而影响对新治疗策略的反应。

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