Neuroblastoma treatment in the post-genomic era.
Neuroblastoma treatment in the post-genomic era.
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DOI：
10.1186/s12929-017-0319-y
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发表时间：
2017-02-08
影响因子：
11
通讯作者：
Tonini GP
中科院分区：
文献类型：
--
作者：
Esposito MR;Aveic S;Seydel A;Tonini GP
神经母细胞瘤是一种起源于神经脊细胞的儿童早期胚胎恶性肿瘤，具有不同的生物学、形态、遗传和临床特征。神经母细胞瘤患者在风险组(低、中、高和超高)中的正确分层对于患者的适当治疗至关重要。OMICS学科中的高通量技术正在导致对神经母细胞瘤分子发病机制的重大洞察。然而，对Omics数据的进一步研究对于更好地描述神经母细胞瘤的肿瘤生物学是必要的。在这篇综述中，我们报告了神经母细胞瘤临床前试验和/或I-II期试验中使用的化合物的最新进展。此外，我们总结了一些与神经母细胞瘤相关的靶向蛋白的化合物：MYCN(直接和间接抑制物)及其下游靶点，Trk，ALK及其下游信号通路。特别是对于后者，考虑到神经母细胞瘤患者ALK基因失控的频率，我们讨论了第二代临床前或临床阶段的ALK抑制剂，用于治疗耐药的神经母细胞瘤患者。我们总结了Omics如何推动神经母细胞瘤治疗的临床试验，以及对生物靶标的研究在多大程度上对个性化药物有用。最后，我们给出了OMICS调查选择的最新药物靶点的概述，并讨论了OMICS的结果如何为我们克服肿瘤耐药性提供了额外的优势。
Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients. High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology. In the present review, we report an update of compounds that are used in preclinical tests and/or in Phase I-II trials for neuroblastoma. Furthermore, we recapitulate a number of compounds targeting proteins associated to neuroblastoma: MYCN (direct and indirect inhibitors) and downstream targets, Trk, ALK and its downstream signalling pathways. In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib. We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine. Finally, we give an overview of the most recent druggable targets selected by Omics investigation and discuss how the Omics results can provide us additional advantages for overcoming tumour drug resistance.