Translational implications of tumor heterogeneity.
Translational implications of tumor heterogeneity.
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DOI：
10.1158/1078-0432.ccr-14-1429
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发表时间：
2015-03-15
期刊：
影响因子：
--
通讯作者：
Swanton C
中科院分区：
文献类型：
--
作者：
Jamal-Hanjani M;Quezada SA;Larkin J;Swanton C
下一代测序和生物信息学的进步带来了对癌症基因组及其演变的前所未有的看法。基因组研究已经证明了不同起源的肿瘤的复杂和异质性克隆景观，以及肿瘤内异质性对治疗反应和抗性、癌症进展和疾病复发风险的潜在影响。然而，亚克隆突变的重要性，特别是驱动基因的突变，以及它们随时间的演变和它们对癌症治疗的反应动力学，尚未确定。现在有必要的工具来前瞻性地确定克隆异质性是否可以用作临床结果的生物标志物，以及亚克隆体细胞改变在多大程度上可能影响临床结果。采用纵向组织取样的研究，整合基因组和临床数据，有可能揭示亚克隆组成并跟踪肿瘤的演变，以解决这些问题，并开始定义不同肿瘤类型中遗传多样性的广度及其与患者结局的相关性。这些研究可能为新的耐药机制提供进一步的证据，为置于肿瘤进化背景下的新的组合，适应性和肿瘤免疫疗法提供信息。
Advances in next-generation sequencing and bioinformatics have led to an unprecedented view of the cancer genome and its evolution. Genomic studies have demonstrated the complex and heterogeneous clonal landscape of tumors of different origins, and the potential impact of intratumor heterogeneity on treatment response and resistance, cancer progression and the risk of disease relapse. However, the significance of subclonal mutations, in particular mutations in driver genes, and their evolution through time and their dynamics in response to cancer therapies, is yet to be determined. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome, and to what extent subclonal somatic alterations might influence clinical outcome. Studies that employ longitudinal tissue sampling, integrating both genomic and clinical data, have the potential to reveal the subclonal composition and track the evolution of tumors in order to address these questions, and to begin to define the breadth of genetic diversity in different tumor types, and its relevance to patient outcome. Such studies may provide further evidence for novel drug resistance mechanisms informing novel combinatorial, adaptive and tumour immune-therapies placed within the context of tumor evolution.