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癌症中的细胞可塑性:遗传、表观遗传机制和肿瘤微环境的复杂相互作用。

Cell plasticity in cancer: A complex interplay of genetic, epigenetic mechanisms and tumor micro-environment.

机构信息

Clinical Associate Professor of Surgery, Department of Surgery, Kansas City VA Medical Center, University of Missouri Kansas City, USA; Cancer Biology and Therapeutics, HMS High-Impact Cancer Research (HI-CR) Program, Harvard Medical School 2018-2019, USA.

出版信息

Surg Oncol. 2020 Sep;34:154-162. doi: 10.1016/j.suronc.2020.04.017. Epub 2020 Apr 22.

Abstract

Cell plasticity, also known as lineage plasticity is defined as the ability of a cell to reprogram and change its phenotype identity. Cell plasticity is context dependent and occurs during the development of an embryo, tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors cells exhibit varying forms of cell plasticity in each stage of the disease to evade normal regulation as would have occurred in normal cell division and homeostasis. Current evidence demonstrates complex interplay between the genes, epigenes, tumor microenvironment and the EMT in cell reprogramming and cancer cell plasticity. Herein we present experimental evidence and evolving new developments in cell plasticity in cancer cells. Additionally "Deregulated/aberrant/hijacked cell plasticity" could be considered as an additional hallmark of a cancer. In the future, combining the advances in next generation sequencing and single cell RNA techniques with evolving AI (artificial intelligence) technologies such as deep learning techniques may predict the trajectories of cancer cells and assist in navigating through the complex intricacies of the cancers. A durable, precise, personalized oncologic treatment could be a reality.

摘要

细胞可塑性,也称为谱系可塑性,定义为细胞重新编程和改变其表型特征的能力。细胞可塑性取决于上下文,并且发生在胚胎发育、组织再生、伤口愈合过程中。然而,当细胞可塑性失调和异常时,它也会导致癌症的发生、进展、转移和对治疗的耐药性。肿瘤细胞在疾病的每个阶段都表现出不同形式的细胞可塑性,以逃避正常的调节,就像正常细胞分裂和体内平衡时那样。目前的证据表明,基因、表观遗传学、肿瘤微环境和 EMT 在细胞重编程和癌细胞可塑性中相互作用复杂。本文介绍了癌细胞可塑性的实验证据和新的发展。此外,“失调/异常/劫持的细胞可塑性”可以被视为癌症的另一个标志。在未来,将下一代测序和单细胞 RNA 技术的进展与新兴的人工智能 (AI) 技术(如深度学习技术)相结合,可能会预测癌细胞的轨迹,并帮助人们在癌症的复杂细节中进行导航。持久、精确、个性化的肿瘤治疗可能成为现实。

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