University of Alabama, Birmingham, Birmingham, AL 35233, USA.
Anticancer Agents Med Chem. 2013 May;13(4):563-75. doi: 10.2174/1871520611313040005.
Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Neuroblastoma tumorigenesis and malignant transformation is driven by overexpression and dominance of cell survival pathways and a lack of normal cellular senescence or apoptosis. Therefore, manipulation of cell survival pathways may decrease the malignant potential of these tumors and provide avenues for the development of novel therapeutics. This review focuses on several facets of cell survival pathways including protein kinases (PI3K, AKT, ALK, and FAK), transcription factors (NF-κB, MYCN and p53), and growth factors (IGF, EGF, PDGF, and VEGF). Modulation of each of these factors decreases the growth or otherwise hinders the malignant potential of neuroblastoma, and many therapeutics targeting these pathways are already in the clinical trial phase of development. Continued research and discovery of effective modulators of these pathways will revolutionize the treatment of neuroblastoma.
神经母细胞瘤是儿童期最常见的颅外实体瘤,占儿童癌症死亡人数的 15%以上。神经母细胞瘤的发生和恶性转化是由细胞存活途径的过度表达和优势驱动的,而缺乏正常的细胞衰老或细胞凋亡。因此,对细胞存活途径的操纵可能会降低这些肿瘤的恶性潜能,并为开发新的治疗方法提供途径。本综述重点介绍了细胞存活途径的几个方面,包括蛋白激酶(PI3K、AKT、ALK 和 FAK)、转录因子(NF-κB、MYCN 和 p53)和生长因子(IGF、EGF、PDGF 和 VEGF)。这些因素中的每一个的调节都可以降低神经母细胞瘤的生长或其他恶性潜能,许多针对这些途径的治疗方法已经处于临床试验开发阶段。对这些途径的有效调节剂的持续研究和发现将彻底改变神经母细胞瘤的治疗方法。