Selection and adaptation during metastatic cancer progression
Selection and adaptation during metastatic cancer progression
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DOI：
10.1038/nature12628
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发表时间：
2013-09-19
期刊：
影响因子：
64.8
通讯作者：
Klein, Christoph A.
中科院分区：
文献类型：
--
作者：
Klein, Christoph A.
癌症通常被认为是由基因组和遗传不稳定性驱动的无性进化过程。按照惯例，突变、选择和适应被认为主要发生在原发性肿瘤内，并且在较小程度上发生在原发性肿瘤外。然而，在“治愈性”手术后残留的播散性癌细胞在转移表现之前表现出极端的基因组异质性。这种异质性后来通过选择性克隆扩增而降低，表明播散的细胞尚未获得完全恶性细胞的关键特征。消除原发性肿瘤外的细胞进展意味着诊断和辅助治疗的新挑战和机会。
Cancer is often regarded as a process of asexual evolution driven by genomic and genetic instability. Mutation, selection and adaptation are by convention thought to occur primarily within, and to a lesser degree outside, the primary tumour. However, disseminated cancer cells that remain after 'curative' surgery exhibit extreme genomic heterogeneity before the manifestation of metastasis. This heterogeneity is later reduced by selected clonal expansion, suggesting that the disseminated cells had yet to acquire key traits of fully malignant cells. Abrogation of the cells' progression outside the primary tumour implies new challenges and opportunities for diagnosis and adjuvant therapies.