Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Cancer Lett. 2013 Sep 10;338(1):174-83. doi: 10.1016/j.canlet.2012.04.020. Epub 2012 Apr 30.
Cancer stem cells (CSCs) are a sub-population of cancer cells that possess characteristics associated with normal stem cells but with the peculiarity that they are tumourigenic. This property allows them to persist in the tumour population, causing relapse and metastasis by giving rise to new tumours. Accordingly, if the CSCs were eliminated, then the tumour would simply regress due to differentiation and cell death. By selectively targeting CSCs, it may be possible to treat patients with aggressive, non-resectable tumours and prevent the tumour from metastasising. MicroRNAs are involved in all biological processes, and several studies have demonstrated their function in human tumourigenesis. Importantly, microRNAs have been implicated in the regulation of stem cells and CSCs. The most important concept to emerge with regard to CSC therapy is still controversial because a number of signalling pathways unique to normal stem cells may also be operating in CSCs, and these offer new targets for therapy. This article reviews how the modulation of microRNAs may revert tumour proliferation in vivo and in vitro and how this approach could be transferred to the clinic. Although the delivery of therapeutic microRNAs to target cells is a challenge that still needs to be overcome, microRNAs offer the advantage that they are small molecules that can be easily transported by body fluids, which makes them good candidates for cancer therapy.
癌症干细胞(CSCs)是癌细胞中的一个亚群,具有与正常干细胞相关的特征,但具有一个特殊性质,即它们具有致瘤性。这种特性使它们能够在肿瘤群体中持续存在,通过产生新的肿瘤导致复发和转移。因此,如果消除 CSCs,那么肿瘤由于分化和细胞死亡就会简单地消退。通过选择性地靶向 CSCs,可能可以治疗具有侵袭性、不可切除的肿瘤的患者,并防止肿瘤转移。 microRNAs 参与所有的生物学过程,并且有几项研究已经证明了它们在人类肿瘤发生中的作用。重要的是,microRNAs 已经被牵涉到干细胞和 CSCs 的调控中。与 CSC 治疗相关的最重要的概念仍然存在争议,因为一些正常干细胞特有的信号通路也可能在 CSCs 中运作,而这些为治疗提供了新的靶点。这篇文章综述了 microRNAs 的调节如何在体内和体外使肿瘤增殖逆转,以及这种方法如何转化为临床应用。尽管将治疗性 microRNAs 递送到靶细胞是一个仍然需要克服的挑战,但 microRNAs 具有优势,即它们是小分子,可以通过体液轻松运输,这使它们成为癌症治疗的良好候选物。