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人类癌症的小鼠模型:精准肿瘤学中转译的时效性。

Mouse avatars of human cancers: the temporality of translation in precision oncology.

机构信息

Section for History and Philosophy of Science, Department of Science Education, University of Copenhagen, Niels Bohr Building (NBB), Universitetsparken 5, 2100, Copenhagen Ø, Denmark.

Department of Public Health, Centre for Medical Science and Technology Studies, University of Copenhagen, Oester Farimagsgade 5, opg. B, Postboks 2099, 1014, Copenhagen, Denmark.

出版信息

Hist Philos Life Sci. 2021 Feb 23;43(1):27. doi: 10.1007/s40656-021-00383-w.

Abstract

Patient-derived xenografts (PDXs) are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called "mouse avatars", PDXs are hoped to allow for patient-specific drug testing in real-time (in parallel to treatment of the corresponding cancer patient). This paper examines the circulation of knowledge and bodily material across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention.

摘要

患者来源异种移植(PDX)目前被推广为精准肿瘤学中的新型转化模型。PDX 是带有人类肿瘤的免疫缺陷小鼠,被用作替代模型来代表特定类型的癌症。通过考虑癌症肿瘤的遗传异质性,PDX 有望在临床前研究中提供更具临床相关性的结果。此外,在所谓的“老鼠替身”的作用下,PDX 有望允许实时进行患者特异性药物测试(与相应癌症患者的治疗同时进行)。本文从历史和当代实践两个方面考察了人类和个性化小鼠模型物种边界上的知识和身体物质的循环。PDX 提出了关于动物模型和人类患者之间关系的有趣问题,以及杂交或种间模型是否有能力弥合现有的转化差距。我们强调,PDX 的转化潜力不仅取决于模型和目标的代表性匹配,还取决于模型开发和实际用途之间的时间对准。除了确保人类肿瘤在鼠体内的时间稳定性的重要性之外,鼠标替身概念还基于将临床和实验室的时间范围对齐的可能性。我们研究了解决时间挑战的策略,包括冷冻保存和生物库,以及通过修改和使用发展更快的生物体来加速转化的尝试。我们讨论了如何随着精准肿瘤学的发展改变模型的特点,并且认为时间性是值得更多哲学关注的模型特点。

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