Neuroblastoma (NB) is the most prevalent extracranial childhood tumor and the third leading cause of death from cancer in children. Despite having a high overall survival rate for low- and intermediate-risk patients, survival rates for high-risk cases remain unsatisfactory. The current standard treatment for high-risk NB involves surgery, chemotherapy, radiotherapy, autologous stem cell transplantation, immunotherapy with anti-ganglioside GD2, and differentiation therapy with isotretinoin. Besides not being enough to achieve a high survival rate in high-risk patients, these treatments are associated with significant side effects. With next-generation sequencing technologies, a better understanding of the genetic and epigenetic landscapes of NB has been achieved. This has led to the study of novel treatments to improve the overall survival rate of high-risk NB and reduce the toxicity of conventional treatments. Current research is focusing on the development of targeted drugs for genetic and epigenetic alterations, and protein degraders. Moreover, immunotherapy to enhance anticancer immune responses and by using cell-engineering techniques with chimeric antigen receptor (CAR) T and NK cells are being explored to target NB cells. Here, we review promising novel treatment strategies for NB, which target genetics, epigenetics, the tumor microenvironment, and the immune landscape, highlighting preclinical studies and ongoing clinical trials.
神经母细胞瘤（NB）是最常见的儿童颅外肿瘤，也是儿童癌症死亡的第三大原因。尽管低危和中危患者的总体生存率较高，但高危病例的生存率仍不理想。目前高危NB的标准治疗包括手术、化疗、放疗、自体干细胞移植、抗神经节苷脂GD2免疫治疗以及异维A酸分化治疗。这些治疗方法不仅不足以使高危患者获得较高的生存率，还会伴随显著的副作用。随着下一代测序技术的发展，人们对NB的遗传和表观遗传特征有了更深入的理解，从而推动了新型治疗方法的研究，旨在提高高危NB的总体生存率并降低传统治疗的毒性。当前研究重点聚焦于针对遗传和表观遗传改变以及蛋白质降解剂的靶向药物开发。此外，通过利用嵌合抗原受体（CAR）T细胞和NK细胞的细胞工程技术，增强抗癌免疫反应的免疫疗法也正在探索中，以靶向NB细胞。本文综述了针对遗传学、表观遗传学、肿瘤微环境和免疫环境的有前景的新型NB治疗策略，重点介绍了临床前研究和正在进行的临床试验。
Interplay Between the Epigenome, the Microenvironment, and the Immune System in Neuroblastoma
肿瘤(癌症)患者之家