Division of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan.
Cells. 2013 Jun 20;2(2):432-59. doi: 10.3390/cells2020432.
Neuroblastoma (NB) is one of the most common malignant solid tumors in childhood, which derives from the sympathoadrenal lineage of the neural crest and exhibits extremely heterogeneous biological and clinical behaviors. The infant patients frequently undergo spontaneous regression even with metastatic disease, whereas the patients of more than one year of age who suffer from disseminated disease have a poor outcome despite intensive multimodal treatment. Spontaneous regression in favorable NBs has been proposed to be triggered by nerve growth factor (NGF) deficiency in the tumor with NGF dependency for survival, while aggressive NBs have defective apoptotic machinery which enables the tumor cells to evade apoptosis and confers the resistance to treatment. This paper reviews the molecules and pathways that have been recently identified to be involved in apoptotic cell death in NB and discusses their potential prospects for developing more effective therapeutic strategies against aggressive NB.
神经母细胞瘤(NB)是儿童期最常见的恶性实体肿瘤之一,起源于神经嵴交感肾上腺系,表现出极其异质的生物学和临床行为。婴儿患者即使患有转移性疾病也经常自发消退,而 1 岁以上患有播散性疾病的患者尽管接受了强化多模式治疗,预后仍不佳。人们提出,有利的 NB 自发消退是由肿瘤中神经生长因子(NGF)缺乏引起的,肿瘤依赖 NGF 存活,而侵袭性 NB 则存在凋亡机制缺陷,使肿瘤细胞能够逃避凋亡,并对治疗产生耐药性。本文综述了最近发现的参与 NB 细胞凋亡的分子和途径,并讨论了它们在开发针对侵袭性 NB 的更有效治疗策略方面的潜在前景。