Game of clones: Battles in the field of carcinogenesis.
Game of clones: Battles in the field of carcinogenesis.
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DOI：
10.1016/j.pharmthera.2022.108251
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发表时间：
2022-09
影响因子：
13.5
通讯作者：
Kadara, Humam
中科院分区：
文献类型：
--
作者：
Rahal, Zahraa;Sinjab, Ansam;Wistuba, Ignacio I.;Kadara, Humam
大量测序方法的最新进展以及单细胞水平的基因组解码揭示了正常组织中惊人的高体细胞突变负担，并增加了我们对“野癌化”图景的理解，即暴露于诱变剂的正常组织中的分子和免疫变化，概括了肿瘤中的变化。绘制正常组织中的体细胞突变情况图可以对我们理解肿瘤是如何从突变的上皮细胞中产生有很大的意义。理解这些突变的意义，以了解从正常上皮、癌前病变到恶性组织的病理连续体的进展，将有助于为识别理想的靶点铺平道路，这些靶点可以指导预防或消除癌症发展的早期阶段的新策略。在这篇综述中，我们将提供野生性癌变的简要历史及其对理解癌症发病机制的早期阶段和偏离病理“正常”状态的意义。这篇综述将概述在正常组织中积累的突变如何导致突变克隆的拼凑，这些突变克隆在保持整体功能稳态的同时相互竞争。该综述还探讨了克隆竞争在指导正常组织命运中的作用，并总结了在这一现象中引发的与癌症发展有关的多种机制。最后，我们强调了了解正常组织中突变的重要性，以及克隆竞争动力学(在上皮和微环境中)及其在探索抗癌新方法方面的重要性。
Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of “field cancerization”, that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium. Making sense of those mutations to understand the progression along the pathologic continuum of normal epithelia, preneoplasias, up to malignant tissues will help pave way for identification of ideal targets that can guide new strategies for preventing or eliminating cancers at their earliest stages of development. In this review, we will provide a brief history of field cancerization and its implications on understanding early stages of cancer pathogenesis and deviation from the pathologically “normal” state. The review will provide an overview of how mutations accumulating in normal tissues can lead to a patchwork of mutated cell clones that compete while maintaining an overall state of functional homeostasis. The review also explores the role of clonal competition in directing the fate of normal tissues and summarizes multiple mechanisms elicited in this phenomenon and which have been linked to cancer development. Finally, we highlight the importance of understanding mutations in normal tissues, as well as clonal competition dynamics (in both the epithelium and the microenvironment) and their significance in exploring new approaches to combatting cancer.
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DOI：
10.1056/nejmoa2201445
发表时间：
2022-06-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1038/s41576-020-0262-8
发表时间：
2020-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Baker NE
通讯作者：
Baker NE
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
影响因子：
64.8
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
通讯作者：
Torres, Miguel
肿瘤前期进展 人类干细胞群体的克隆进化
影响因子：
6
作者：
Calabrese, P;Tavaré, S;Shibata, D
通讯作者：
Shibata, D