Unraveling Tumor Heterogeneity by Using DNA Barcoding Technologies to Develop Personalized Treatment Strategies in Advanced-Stage PDAC.

Unraveling Tumor Heterogeneity by Using DNA Barcoding Technologies to Develop Personalized Treatment Strategies in Advanced-Stage PDAC.
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通过使用DNA条形码技术解开肿瘤异质性,以制定晚期PDAC的个性化治疗策略。

DOI:
10.3390/cancers13164187
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发表时间:
2021-08-20
期刊:
影响因子:
5.2
通讯作者:
Grüner BM
Grüner BM
中科院分区:
医学2区
文献类型:
--
作者:
Dujardin P;Baginska AK;Urban S;Grüner BM

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胰腺癌是最难治疗的癌症之一。这主要是由于其异质性,其中癌细胞的子集具有不同的特性和能力,这些特性和能力决定了它们是否以及如何转移或对治疗作出反应。DNA条形码技术已经成为研究这种异质性的强大工具,因为它们允许标记癌细胞池中的单个肿瘤细胞,并在转移或治疗期间跟踪它们的细胞状态和命运。本综述的目的是概述胰腺癌中不同水平的肿瘤异质性,这些异质性水平可能导致有效的个性化治疗策略的障碍,以及如何应用不同的条形码方法来研究这些重要问题。肿瘤异质性是许多实体瘤(包括胰腺导管腺癌(PDAC))的标志,也是癌症克隆进化的固有结果。因此,它被认为是疾病许多特征的基本概念,包括转移、适应不同微环境和产生耐药性的能力。毫无疑问,PDAC的高死亡率在很大程度上可归因于这些特性。尽管其明显的重要性,研究肿瘤异质性一直是一项具有挑战性的任务,主要是由于其复杂性和缺乏适当的方法。然而,近年来,分子DNA条形码已经成为一种复杂的工具,可以对细胞库中的单个细胞或亚群进行定位,以研究异质性,从而设计出新的个性化治疗策略。在这篇综述中,我们概述了遗传和非遗传的肿瘤间和肿瘤内异质性及其对PDAC(个性化)治疗策略的影响,并讨论了DNA条形码技术如何工作,并可应用于研究这一临床高度相关的问题。
Pancreatic cancer is one of the hardest-to-treat cancers. This is mainly due to its heterogeneity, where subsets of cancer cells possess distinct properties and abilities that determine if and how they metastasize or respond to therapy. DNA barcoding technologies have emerged as a powerful tool to study this heterogeneity, as they allow labeling of individual tumor cells within a cancer cell pool and follow their cellular states and fates during metastasis or upon therapy. The aim of this review was to provide an overview of the various levels of tumor heterogeneity in pancreatic cancer, the obstacles these levels of heterogeneity can cause for effective personalized treatment strategies, and how different barcoding approaches can be applied to study these important questions. Tumor heterogeneity is a hallmark of many solid tumors, including pancreatic ductal adenocarcinoma (PDAC), and an inherent consequence of the clonal evolution of cancers. As such, it is considered the underlying concept of many characteristics of the disease, including the ability to metastasize, adapt to different microenvironments, and to develop therapy resistance. Undoubtedly, the high mortality of PDAC can be attributed to a high extent to these properties. Despite its apparent importance, studying tumor heterogeneity has been a challenging task, mainly due to its complexity and lack of appropriate methods. However, in recent years molecular DNA barcoding has emerged as a sophisticated tool that allows mapping of individual cells or subpopulations in a cell pool to study heterogeneity and thus devise new personalized treatment strategies. In this review, we provide an overview of genetic and non-genetic inter- and intra-tumor heterogeneity and its impact on (personalized) treatment strategies in PDAC and address how DNA barcoding technologies work and can be applied to study this clinically highly relevant question.
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