Clinical Implications of Colorectal Cancer Stem Cells in the Age of Single-Cell Omics and Targeted Therapies.
Clinical Implications of Colorectal Cancer Stem Cells in the Age of Single-Cell Omics and Targeted Therapies.
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结直肠癌干细胞在单细胞组学和靶向治疗时代的临床意义。
DOI：
10.1053/j.gastro.2020.12.080
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发表时间：
2021-05
期刊：
影响因子：
29.4
通讯作者：
Frank NY
中科院分区：
文献类型：
--
作者：
Frank MH;Wilson BJ;Gold JS;Frank NY
癌症干细胞（CSC）的概念源于对固有肿瘤异质性的认识，并表明在给定的肿瘤中，与正常组织类似，存在由少数寿命延长的更原始细胞（即CSC）组成的细胞层次结构，这些细胞产生寿命更短，分化程度更高的细胞（即癌症大量群体），这些细胞本身不能使肿瘤永久存在。CSC可以负责癌症对常规、靶向和免疫治疗方式的治疗抗性，以及通过CSC内在分子机制的癌症进展。结肠直肠癌（CRC）中CSC的存在首先通过在人-小鼠肿瘤异种移植实验中证明该细胞亚群的增强的克隆形成性和肿瘤形成能力来确定，随后通过小鼠中的谱系追踪研究来证实。用于CRC CSC鉴定的表面标志物及其预期分离现已建立。因此，将单细胞组学技术应用于CSC表征，包括全基因组测序、RNA测序和表观遗传学分析，为发现新的靶向分子途径并因此开发用于CRC根除的新策略提供了前所未有的机会。我们回顾了这一领域的最新进展，并讨论了下一代CSC分析对目前批准和实验性靶向CRC治疗的潜在影响。
The cancer stem cell (CSC) concept emerged from the recognition of inherent tumor heterogeneity and suggests that within a given tumor, in analogy to normal tissues, there exists a cellular hierarchy composed of a minority of more primitive cells with enhanced longevity (ie, CSCs) that give rise to shorter-lived, more differentiated cells (ie, cancer bulk populations), which on their own are not capable of tumor perpetuation. CSCs can be responsible for cancer therapeutic resistance to conventional, targeted, and immunotherapeutic treatment modalities, and for cancer progression through CSC-intrinsic molecular mechanisms. The existence of CSCs in colorectal cancer (CRC) was first established through demonstration of enhanced clonogenicity and tumor-forming capacity of this cell subset in human-to-mouse tumor xenotransplantation experiments and subsequently confirmed through lineage-tracing studies in mice. Surface markers for CRC CSC identification and their prospective isolation are now established. Therefore, the application of single-cell omics technologies to CSC characterization, including whole-genome sequencing, RNA sequencing, and epigenetic analyses, opens unprecedented opportunities to discover novel targetable molecular pathways and hence to develop novel strategies for CRC eradication. We review recent advances in this field and discuss the potential implications of next-generation CSC analyses for currently approved and experimental targeted CRC therapies.
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影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
--
作者：
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通讯作者：
Chen Z
影响因子：
6
作者：
Desai A;Yan Y;Gerson SL
通讯作者：
Gerson SL
影响因子：
64.8
作者：
BRUCE, WR;VANDERGA.H
通讯作者：
VANDERGA.H