Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.
Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.
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DOI：
10.1186/s12943-017-0601-3
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发表时间：
2017-02-23
期刊：
影响因子：
37.3
通讯作者：
Gallagher MF
中科院分区：
文献类型：
--
作者：
Gasch C;Ffrench B;O'Leary JJ;Gallagher MF
人们普遍认为，靶向恶性肿瘤的肿瘤起始癌症干细胞（CSC）组分具有巨大的治疗潜力，特别是在治疗抗性疾病中。然而，尽管做出了共同努力，但CSC靶向策略尚未有效地转化为临床。这部分是由于我们对CSC治疗抵抗的机制的不完全理解。特别是，治疗抗性和CSC组织为干细胞-祖细胞-分化细胞层级之间的关系尚未得到广泛研究。在这篇综述中，我们认为，现代的临床策略应该认识到，CSC层次结构是一个动态的目标，包含敏感和耐药的组件，并表示一个集合的治疗耐药机制。我们建议CSC的等级在主要表现的变化，以响应临床干预，导致复发性恶性肿瘤，应针对不同的。因此，将CSC的分层组织纳入我们的床旁理论应该加快CSC目标到床旁实践的翻译。最后，我们讨论了一些策略，通过这些策略，我们可以抓住这些移动的临床目标，以专门损害耐药性疾病。
It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.