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癌症干细胞在胃食管交界腺癌耐药中的作用

The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma.

作者信息

Dinneen Kate, Baird Anne-Marie, Ryan Ciara, Sheils Orla

机构信息

School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

Department of Histopathology, St. James's Hospital, Dublin, Ireland.

出版信息

Front Mol Biosci. 2021 Feb 8;8:600373. doi: 10.3389/fmolb.2021.600373. eCollection 2021.

Abstract

Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20 century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance.

摘要

自20世纪中叶以来,胃食管交界腺癌(GEJA)在西方世界的发病率急剧上升。其预后较差,传统抗癌疗法并不能显著改善生存结果。这些肿瘤由癌干细胞(CSC)和非CSC组成的异质性群体构成,前者在肿瘤发生、转移以及重要的耐药性方面发挥着关键作用。由于CSC具有无限自我复制的能力,它们对抗癌疗法的耐药性成为有效治疗GEJA的重大障碍。正在进行的药物研发项目旨在靶向并根除CSC,然而其特征鉴定以及因此进行的识别却很困难。CSC调控十分复杂,涉及一系列信号通路,而这些信号通路又受到包括上皮间质转化(EMT)、微小RNA(miRNA)、肿瘤微环境和表观遗传修饰等多种因素的影响。CSC的鉴定通常依赖于特定细胞表面标志物的表达,但这些标志物在不同恶性肿瘤之间存在差异,并且实际上常常在非肿瘤组织中共同表达。因此,开发针对CSC的靶向药物疗法需要了解疾病特异性的CSC标志物和调控机制。本综述详细阐述了目前关于GEJA中CSC的知识,特别强调了它们在耐药性中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82ce/7897661/1088807b4b6c/fmolb-08-600373-g001.jpg

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