Key unresolved questions about metastasis

关于肿瘤转移尚未解决的关键问题

转移被认为是导致绝大多数癌症相关死亡的主要原因。然而，我们对肿瘤转移过程的理解仍然非常有限。

• What controls the timing of metastatic dissemination across different cancer types? Are there phenotypic differences between cells that disseminate early or late?

• 是什么控制了不同类型癌症的转移扩散时间？早期和晚期播散的肿瘤细胞之间是否存在表型差异？

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• How does tumour genotype impact mechanisms of      metastasis? Can metastatic ability be predicted prior to actual dissemination?

• 肿瘤的基因型如何影响转移机制？能否在实际肿瘤扩散之前预测转移能力？

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• How representative are circulating tumour cells  (CTCs) of the cells that successfully metastasize? Do the cells that form metastases represent a stochastic subset of disseminated cells, or is strong selection or adaptation required for metastatic outgrowth?

• 循环肿瘤细胞（CTC）在成功转移的细胞中的代表性如何？形成转移的细胞是否代表了播散细胞的随机子集，或者转移性生长是否需要强有力的选择或适应？

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• What factors control the organs to which cancer cells metastasize? How widespread and important are drivers of  organotropism?

• 哪些因素控制着癌症细胞转移到相应的器官？转移的器官嗜性的驱动因素有多广泛和重要？

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• How is dormancy enforced and what drives cancer cell      escape from dormancy? How does dormancy relate to senescence?

• 休眠是如何实施的，是什么促使癌症细胞摆脱休眠的？休眠与衰老有什么关系？

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• Why are the kinetics of metastatic outgrowth so variable from one cancer type to another?

• 为什么不同癌症的转移生长动力学如此多变？

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• What are the interactions between a primary tumour and its metastases, and among different metastases? To what extent do they affect one another?

• 原发性肿瘤与其转移之间以及不同转移之间的相互作用是什么？它们在多大程度上相互影响？

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• How do metastasizing cells evade immune destruction once they leave the primary tumour environment?

• 一旦转移细胞离开原发性肿瘤环境，它们是如何逃避免疫破坏的？

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• How can metastasis be prevented? Can mechanisms of dissemination or escape from dormancy be targeted?

• 如何预防肿瘤转移？肿瘤播散或摆脱休眠的机制是否可以成为防治靶点？

全文链接：https://www.nature.com/articles/s41568-023-00568-4 

参考文献：Hebert, J.D., Neal, J.W. & Winslow, M.M. Dissecting metastasis using preclinical models and methods. Nat Rev Cancer (2023). https://doi.org/10.1038/s41568-023-00568-4