隐藏在视野中:药物诱导肿瘤进化中的表观遗传学可塑性

IF 3.2 Q2 GENETICS & HEREDITY
Ankur Sharma
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引用次数: 5

摘要

癌症是一种异质性疾病,在细胞和分子水平上存在关键差异。在肿瘤发展过程中获得这些差异表现为导致肿瘤多样性的功能和表型异质性,也称为肿瘤内异质性(ITH)。在肿瘤内,存在能够引发和维持肿瘤的细胞亚群。这些细胞通常表现出对标准护理抗癌药物的耐药性。然而,各种亚群(克隆)在耐药性中的作用仍有待研究。此外,耐药性是先前存在的细胞的克隆选择的结果,还是细胞通过表观基因组的动态重组获得耐药性,目前还没有定论。因此,我们研究了药物诱导的头颈部鳞状细胞癌患者来源的原代细胞的肿瘤演变。我们的数据证明了预先存在的稳定表观遗传状态在药物诱导的肿瘤细胞适应性进化中的作用。重要的是,化疗和表观遗传学抑制剂的结合可以预防/延迟药物诱导的肿瘤演变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hiding in Plain Sight: Epigenetic Plasticity in Drug-Induced Tumor Evolution
Cancer is a heterogeneous disease with key differences at the cellular and molecular levels. Acquisition of these differences during the course of tumor development manifests into functional and phenotypic heterogeneity leading to tumor diversity, also referred to as intra-tumor heterogeneity (ITH). Within a tumor, there are subpopulations of cells capable of tumor initiation and maintenance. These cells often exhibit resistance to standard-of-care anti-cancer drugs. However, the role of various subpopulations (clones) in drug resistance remains to be investigated. Moreover, the jury is still out about whether drug resistance is a result of clonal selection of preexisting cells, or the cells acquire resistance by dynamic re-wiring of their epigenome. Therefore, we investigated the drug-induced tumor evolution in patient-derived primary cells of head and neck squamous cell carcinoma. Our data demonstrated the role of a preexisting poised epigenetic state in drug-induced adaptive evolution of tumor cells. Importantly, the combination of chemotherapy and epigenetic inhibitors can prevent/delay drug-induced tumor evolution.
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来源期刊
Epigenetics Insights
Epigenetics Insights GENETICS & HEREDITY-
CiteScore
5.10
自引率
0.00%
发文量
10
审稿时长
8 weeks
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