Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumours that originate from cells of neural crest (NC) origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage. Therapeutic resistance, post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell (CSC)-like subpopulations, which through their self-renewing capacity, intermittent and slow cell cycles, drug-resistant and reversibly adaptive plastic phenotypes, represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs. In this review, dedicated to NB CSCs and the prospects for their therapeutic eradication, we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction, specification, epithelial to mesenchymal transition and migratory behaviour, in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB. We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs, before providing a comprehensive review of the salient molecules, signalling pathways, mechanisms, tumour microenvironmental and therapeutic conditions involved in promoting, selecting and maintaining NB CSC subpopulations, and that underpin their therapy-resistant, self-renewing metastatic behaviour. Finally, we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance, post-therapeutic relapse and metastatic progression.

中文翻译：

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涉及选择和维持神经母细胞瘤癌症干细胞群的机制以及治疗靶向的前景。

儿童神经母细胞瘤 (NB) 是一种异质性、侵袭性、耐药性胚胎肿瘤，起源于神经嵴 (NC) 来源的细胞，特别是属于交感肾上腺祖细胞谱系的神经母细胞。治疗耐药、治疗后复发和随后的转移性 NB 进展主要由癌症干细胞 (CSC) 样亚群驱动，这些亚群通过其自我更新能力、间歇性和缓慢的细胞周期、耐药性和可逆适应性塑料表型，代表改善不利 NB 治疗效果的最重要障碍。在这篇综述中，致力于 NB CSC 及其治疗根除的前景，我们首先简要描述了独特的瞬时脊椎动物胚胎 NC 结构和涉及 NC 诱导、规范、上皮间质转化和迁移行为的显着分子主角，以便让读者熟悉胚胎细胞和分子起源以及 NB 的背景。接下来，我们介绍 NB 和 NB 的潜在 NC 衍生干细胞/祖细胞起源，然后对促进、选择和维持 NB CSC 亚群所涉及的显着分子、信号通路、机制、肿瘤微环境和治疗条件进行全面综述，这支撑了它们的治疗抵抗、自我更新的转移行为。最后，我们回顾了针对和根除 NB 治疗耐药、治疗后复发和转移进展的这些堡垒的潜在治疗策略和未来前景。