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Identification and targeting of cancer stem cells

机译:癌症干细胞的鉴定和靶向

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摘要

Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self-renewal and give rise to bulk populations of non-tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker-specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof-of-principle for the potential therapeutic utility of the CSC concept has recently beenprovided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC-targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC.
机译:癌症干细胞 (CSC) 代表分层组织肿瘤中的恶性细胞亚群,这些肿瘤具有选择性地能够肿瘤起始和自我更新,并通过分化产生大量非致瘤性癌细胞后代。在竞争性肿瘤发展模型中,使用分子定义的癌症亚群的标记特异性遗传谱系跟踪,已经产生了在癌症大批人群中存在前瞻性可识别 CSC 的有力证据。此外,还发现了将CSC与癌症治疗耐药性和临床肿瘤进展联系起来的新机制和关系。重要的是,最近通过证明通过前瞻性分子标记物选择性杀死 CSC 可以抑制肿瘤生长,从而证明了 CSC 概念的潜在治疗效用的原理验证。在此,我们回顾了这些新颖且具有转化相关性的研究进展,并讨论了在 CSC 中优先起作用的耐药机制和分子通路背景下 CSC 靶向治疗的潜在策略。

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