Children's Hospital of Philadelphia, Division of Oncology , CTRB Rm. 3018, 3501 Civic Center Blvd., Philadelphia, PA 19104-4302 , USA +1 215 590 2817 ; +1 215 590 3770 ;
Expert Opin Ther Targets. 2014 Mar;18(3):277-92. doi: 10.1517/14728222.2014.867946. Epub 2014 Jan 6.
Neuroblastoma (NB) is the most common and deadly solid tumor in children. Despite recent improvements, the long-term outlook for high-risk NB is still < 50%. Further, there is considerable short- and long-term toxicity. More effective, less toxic therapy is needed, and the development of targeted therapies offers great promise.
Relevant literature was reviewed to identify current and future therapeutic targets that are critical to malignant transformation and progression of NB. The potential or actual NB therapeutic targets are classified into four categories: i) genes activated by amplification, mutation, translocation or autocrine overexpression; ii) genes inactivated by deletion, mutation or epigenetic silencing; iii) membrane-associated genes expressed on most NBs but few other tissues; or iv) common target genes relevant to NB as well as other tumors.
Therapeutic approaches have been developed to some of these targets, but many remain untargeted at the present time. It is unlikely that single targeted agents will be sufficient for long-term cure, at least for high-risk NBs. The challenge will be how to integrate targeted agents with each other and with conventional therapy to enhance their efficacy, while simultaneously reducing systemic toxicity.
神经母细胞瘤（NB）是儿童中最常见且致命的实体瘤。尽管最近有所改善，但高危 NB 的长期预后仍<50%。此外，还存在相当大的短期和长期毒性。需要更有效、毒性更小的治疗方法，而靶向治疗的发展带来了巨大的希望。
为了确定对 NB 的恶性转化和进展至关重要的当前和未来治疗靶点，我们回顾了相关文献。潜在或实际的 NB 治疗靶点分为四类：i）扩增、突变、易位或自分泌过度表达激活的基因；ii）缺失、突变或表观遗传沉默失活的基因；iii）大多数 NB 上表达但其他组织很少表达的膜相关基因；或 iv）与 NB 以及其他肿瘤相关的常见靶基因。
已经针对其中一些靶点开发了治疗方法，但目前仍有许多靶点未被靶向。单种靶向药物不太可能足以长期治愈，至少对于高危 NB 是如此。挑战将是如何将靶向药物彼此整合，并与常规治疗相结合，以提高疗效，同时降低全身毒性。
