Spontaneous regression of neuroblastoma.
Spontaneous regression of neuroblastoma.
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DOI：
10.1007/s00441-017-2761-2
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发表时间：
2018-05
影响因子：
3.6
通讯作者：
Brodeur GM
中科院分区：
文献类型：
--
作者：
Brodeur GM
神经母细胞瘤的特点是异质性的临床行为，从自发退化或分化为良性神经节细胞瘤，无情的进展，尽管积极的，多模态治疗。事实上，神经母细胞瘤在人类癌症中是独特的，因为它倾向于经历自发消退。最有力的证据来自日本、北美和欧洲进行的大规模筛查研究，在4S期疾病的婴儿中最为明显。这种倾向与以全染色体获得而不是节段染色体变化为特征的基因组变化模式相关，但自发消退的潜在机制目前只是推测。有证据支持神经母细胞瘤自发消退的几种可能机制：（1）神经营养因子剥夺，（2）端粒酶活性丧失，（3）体液或细胞免疫和（4）表观遗传调节的改变和可能的其他机制。更好地理解自发消退的机制可能有助于确定这些肿瘤的靶向治疗方法。最容易靶向的机制是由原肌球蛋白受体激酶A（TrkA）途径调节的发育性程序性细胞死亡的延迟激活。Pan-Trk抑制剂目前正在临床试验中，因此Trk抑制可能被用作患有需要治疗的生物学上有利的肿瘤的婴儿的一线治疗。替代方法包括打破对肿瘤抗原的免疫耐受，但端粒缩短或表观遗传调节的方法不容易药物化。不同的机制自发神经母细胞瘤消退在这里进行审查，沿着可能的治疗方法。
Neuroblastomas are characterized by heterogeneous clinical behavior, from spontaneous regression or differentiation into a benign ganglioneuroma, to relentless progression despite aggressive, multimodality therapy. Indeed, neuroblastoma is unique among human cancers in terms of its propensity to undergo spontaneous regression. The strongest evidence for this comes from the mass screening studies conducted in Japan, North America and Europe and it is most evident in infants with stage 4S disease. This propensity is associated with a pattern of genomic change characterized by whole chromosome gains rather than segmental chromosome changes but the mechanism(s) underlying spontaneous regression are currently a matter of speculation. There is evidence to support several possible mechanisms of spontaneous regression in neuroblastomas: (1) neurotrophin deprivation, (2) loss of telomerase activity, (3) humoral or cellular immunity and (4) alterations in epigenetic regulation and possibly other mechanisms. It is likely that a better understanding of the mechanisms of spontaneous regression will help to identify targeted therapeutic approaches for these tumors. The most easily targeted mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A (TrkA) pathway. Pan-Trk inhibitors are currently in clinical trials and so Trk inhibition might be used as the first line of therapy in infants with biologically favorable tumors that require treatment. Alternative approaches consist of breaking immune tolerance to tumor antigens but approaches to telomere shortening or epigenetic regulation are not easily druggable. The different mechanisms of spontaneous neuroblastoma regression are reviewed here, along with possible therapeutic approaches.
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影响因子：
8
作者：
Astuti, D;Agathanggelou, A;Latif, F
通讯作者：
Latif, F
影响因子：
3.9
作者：
Brodeur, GM;Nakagawara, A;Evans, AE
通讯作者：
Evans, AE
DOI：
10.1158/1078-0432.ccr-08-1815
发表时间：
2009-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brodeur GM;Minturn JE;Ho R;Simpson AM;Iyer R;Varela CR;Light JE;Kolla V;Evans AE
通讯作者：
Evans AE
影响因子：
6.6
作者：
Benard, Jean;Raguenez, Gilda;Valteau-Couanet, Dominique
通讯作者：
Valteau-Couanet, Dominique
影响因子：
45.3
作者：
BRODEUR, GM;PRITCHARD, J;VOUTE, PA
通讯作者：
VOUTE, PA