The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome.
The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome.
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DOI：
10.1186/s12916-017-0900-y
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发表时间：
2017-07-18
期刊：
影响因子：
9.3
通讯作者：
Swanton C
中科院分区：
文献类型：
--
作者：
Caswell DR;Swanton C
快速和廉价测序技术的出现使科学家能够破译原发性肿瘤内，原发性和转移部位之间以及转移之间的异质性。绘制个体肿瘤的进化史揭示了肿瘤异质性的驱动因素，并强调了其对治疗结果的影响。科学家们正在使用改进的测序技术来解决和应对肿瘤异质性的挑战，这是耐药性和复发的主要原因。异源性肿瘤可能通过选择罕见的、侵袭性的、体细胞改变的细胞来促进转移。然而，导致肿瘤内异质性的极端水平的染色体不稳定性与改善的患者结局相关，表明基因组不稳定性的高水平和低水平之间存在微妙的平衡。我们回顾了肿瘤内异质性影响肿瘤演变的证据，包括转移、耐药性和免疫反应。我们讨论了肿瘤异质性的患病率，以及它是如何启动和维持外部和内部力量。了解肿瘤的演变和转移可以产生新的疗法，利用免疫系统来控制新出现的肿瘤新抗原。
The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes. Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse. Heterogeneity may fuel metastasis through the selection of rare, aggressive, somatically altered cells. However, extreme levels of chromosomal instability, which contribute to intratumour heterogeneity, are associated with improved patient outcomes, suggesting a delicate balance between high and low levels of genome instability. We review evidence that intratumour heterogeneity influences tumour evolution, including metastasis, drug resistance, and the immune response. We discuss the prevalence of tumour heterogeneity, and how it can be initiated and sustained by external and internal forces. Understanding tumour evolution and metastasis could yield novel therapies that leverage the immune system to control emerging tumour neo-antigens.
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影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Birkbak NJ;Eklund AC;Li Q;McClelland SE;Endesfelder D;Tan P;Tan IB;Richardson AL;Szallasi Z;Swanton C
通讯作者：
Swanton C
DOI：
10.1126/science.1253462
发表时间：
2014-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Bruin EC;McGranahan N;Mitter R;Salm M;Wedge DC;Yates L;Jamal-Hanjani M;Shafi S;Murugaesu N;Rowan AJ;Grönroos E;Muhammad MA;Horswell S;Gerlinger M;Varela I;Jones D;Marshall J;Voet T;Van Loo P;Rassl DM;Rintoul RC;Janes SM;Lee SM;Forster M;Ahmad T;Lawrence D;Falzon M;Capitanio A;Harkins TT;Lee CC;Tom W;Teefe E;Chen SC;Begum S;Rabinowitz A;Phillimore B;Spencer-Dene B;Stamp G;Szallasi Z;Matthews N;Stewart A;Campbell P;Swanton C
通讯作者：
Swanton C
影响因子：
82.9
作者：
Andor N;Graham TA;Jansen M;Xia LC;Aktipis CA;Petritsch C;Ji HP;Maley CC
通讯作者：
Maley CC