普佳睿 童强松

普佳睿, 童强松. 神经母细胞瘤研究前沿及思考[J]. 中国肿瘤临床, 2023, 50(9): 448-452. doi: 10.12354/j.issn.1000-8179.2023.20221330
引用本文: 普佳睿, 童强松. 神经母细胞瘤研究前沿及思考[J]. 中国肿瘤临床, 2023, 50(9): 448-452. doi: 10.12354/j.issn.1000-8179.2023.20221330
Jiarui Pu, Qiangsong Tong. Research frontiers and reflections on neuroblastoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(9): 448-452. doi: 10.12354/j.issn.1000-8179.2023.20221330
Citation: Jiarui Pu, Qiangsong Tong. Research frontiers and reflections on neuroblastoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(9): 448-452. doi: 10.12354/j.issn.1000-8179.2023.20221330


doi: 10.12354/j.issn.1000-8179.2023.20221330
基金项目: 本文课题受国家自然科学基金项目(编号:81772967、81874085和82072801)资助



    童强松 qs_tong@126.com

Research frontiers and reflections on neuroblastoma

Funds: This work was supported by National Natural Science Foundation of China (No. 81772967, No. 81874085, No. 82072801)
More Information
  • 摘要: 神经母细胞瘤(neuroblastoma,NB)是儿童最常见的颅内实体肿瘤,发现时常常已是晚期,易发生转移,高危NB患儿即使接受高强度治疗,仍可出现复发或转移,治疗效果差。目前NB的发病机制及治疗等已成为儿童实体恶性肿瘤研究的热点、难点。近年来,随着单细胞测序等各种技术手段的进步,NB的发病机制、治疗手段等相关研究取得了诸多进展。本文将对近年来NB的研究进展进行文献综述,阐述了NB的起源、分子遗传学调控机制及免疫学调控机制研究成果,并介绍NB单克隆抗体、肿瘤疫苗、过继细胞疗法及小分子抑制剂的最新进展。


  • [1] van Groningen T, Koster J, Valentijn LJ, et al. Neuroblastoma is composed of two super-enhancer-associated differentiation states[J]. Nat Genet, 2017, 49(8):1261-1266. doi: 10.1038/ng.3899
    [2] Boeva V, Louis-Brennetot C, Peltier A, et al. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries[J]. Nat Genet, 2017, 49(9):1408-1413. doi: 10.1038/ng.3921
    [3] Dong R, Yang R, Zhan Y, et al. Single-cell characterization of malignant phenotypes and developmental trajectories of adrenal neuroblastoma[J]. Cancer Cell, 2020, 38(5):716-733. doi: 10.1016/j.ccell.2020.08.014
    [4] Jansky S, Sharma AK, Korber V, et al. Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma[J]. Nat Genet, 2021, 53(5):683-693.
    [5] Kameneva P, Artemov AV, Kastriti ME, et al. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin[J]. Nat Genet, 2021, 53(5):694-706. doi: 10.1038/s41588-021-00818-x
    [6] Guan JK, Hallberg B, Palmer RH. Chromosome imbalances in neuroblastoma-recent molecular insight into chromosome 1p-deletion, 2p-gain, and 11q-deletion identifies new friends and foes for the future[J]. Cancers, 2021, 13(23):5897. doi: 10.3390/cancers13235897
    [7] García-López J, Wallace K, Otero JH, et al. Large 1p36 deletions affecting Arid1a locus facilitate mycn-driven oncogenesis in neuroblastoma[J]. Cell Rep, 2020, 30(2):454-464. doi: 10.1016/j.celrep.2019.12.048
    [8] Lopez G, Conkrite KL, Doepner M, et al. Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma[J]. Genome Res, 2020, 30(9):1228-1242.
    [9] Keane S, Améen S, Lindlöf A, et al. Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival[J]. Cell Commun Signal, 2020, 18(1):65. doi: 10.1186/s12964-020-00553-6
    [10] Siaw JT, Javanmardi N, van den Eynden J, et al. 11q deletion or ALK activity curbs DLG2 expression to maintain an undifferentiated state in neuroblastoma[J]. Cell Rep, 2020, 32(12):108171. doi: 10.1016/j.celrep.2020.108171
    [11] Javanmardi N, Fransson S, Djos A, et al. Analysis of ALK, MYCN, and the ALK ligand ALKAL2 (FAM150B/AUGα) in neuroblastoma patient samples with chromosome arm 2p rearrangements[J]. Genes Chromosomes Cancer, 2020, 59(1):50-57. doi: 10.1002/gcc.22790
    [12] Borenäs M, Umapathy G, Lai WY, et al. ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation[J]. EMBO J, 2021, 40(3):e105784.
    [13] Milosevic J, Treis D, Fransson S, et al. PPM1D is a therapeutic target in childhood neural tumors[J]. Cancers, 2021, 13(23):6042. doi: 10.3390/cancers13236042
    [14] Rosswog C, Bartenhagen C, Welte A, et al. Chromothripsis followed by circular recombination drives oncogene amplification in human cancer[J]. Nat Genet, 2021, 53(12):1673-1685. doi: 10.1038/s41588-021-00951-7
    [15] Braoudaki M, Hatziagapiou K, Zaravinos A, et al. MYCN in neuroblastoma: “old wine into new wineskins”[J]. Diseases, 2021, 9(4):78.
    [16] Pearson ADJ, Barry E, Mossé YP, et al. Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: accelerate in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration[J]. Eur J Cancer, 2021, 157:198-213. doi: 10.1016/j.ejca.2021.08.022
    [17] Alaminos M, Davalos V, Cheung NKV, et al. Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma[J]. J Natl Cancer Inst, 2004, 96(16):1208-1219. doi: 10.1093/jnci/djh224
    [18] Zhu TY, Liu J, Beck S, et al. A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution[J]. Nat Methods, 2022, 19(3):296-306. doi: 10.1038/s41592-022-01412-7
    [19] Phimmachanh M, Han JZR, O'Donnell YEI, et al. Histone deacetylases and histone deacetylase inhibitors in neuroblastoma[J]. Front Cell Dev Biol, 2020, 8:578770.
    [20] Huang L, Zhang XO, Rozen EJ, et al. PRMT5 activates AKT via methylation to promote tumor metastasis[J]. Nat Commun, 2022, 13(1):3955. doi: 10.1038/s41467-022-31645-1
    [21] Pottoo FH, Barkat MA, Harshita, et al. Nanotechnological based miRNA intervention in the therapeutic management of neuroblastoma[J]. Semin Cancer Biol, 2021, 69:100-108. doi: 10.1016/j.semcancer.2019.09.017
    [22] Zhong X, Zhang Y, Wang L, et al. Cellular components in tumor microenvironment of neuroblastoma and the prognostic value[J]. Peer J, 2019, 7:e8017.
    [23] Aiken TJ, Erbe AK, Zebertavage L, et al. Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma[J]. J Immunother Cancer, 2022, 10(5):e004834.
    [24] Pathania AS, Prathipati P, Murakonda SP, et al. Immune checkpoint molecules in neuroblastoma: a clinical perspective[J]. Semin Cancer Biol, 2022, 86(Pt 2):247-258.
    [25] Wienke J, Dierselhuis MP, Tytgat GAM, et al. The immune landscape of neuroblastoma: challenges and opportunities for novel therapeutic strategies in pediatric oncology[J]. Eur J Cancer, 2021, 144:123-150. doi: 10.1016/j.ejca.2020.11.014
    [26] Yu AL, Gilman AL, Ozkaynak MF, et al. Long-term follow-up of a phase III study of ch14.18 (dinutuximab)+cytokine immunotherapy in children with high-risk neuroblastoma: COG study ANBL0032[J]. Clin Cancer Res, 2021, 27(8): 2179-2189.
    [27] Park JA, Cheung NKV. Targets and antibody formats for immunotherapy of neuroblastoma[J]. J Clin Oncol, 2020, 38(16):1836-1848. doi: 10.1200/JCO.19.01410
    [28] Cheung IY, Cheung NKV, Modak S, et al. Survival impact of anti-GD2 antibody response in a phase II ganglioside vaccine trial among patients with high-risk neuroblastoma with prior disease progression[J]. J Clin Oncol, 2021, 39(3):215-226. doi: 10.1200/JCO.20.01892
    [29] Stegantseva MV, Shinkevich VA, Tumar EM, et al. Multi-antigen DNA vaccine delivered by polyethylenimine and Salmonella enterica in neuroblastoma mouse model[J]. Cancer Immunol Immunother, 2020, 69(12):2613-2622. doi: 10.1007/s00262-020-02652-2
    [30] Heitzeneder S, Bosse KR, Zhu Z, et al. GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity[J]. Cancer Cell, 2022, 40(1):53-69.
    [31] Quamine AE, Olsen MR, Cho MM, et al. Approaches to enhance natural killer cell-based immunotherapy for pediatric solid tumors[J]. Cancers, 2021, 13(11):2796.
    [32] Jonus HC, Burnham RE, Ho A, et al. Dissecting the cellular components of ex vivo γδ T cell expansions to optimize selection of potent cell therapy donors for neuroblastoma immunotherapy trials[J]. Oncoimmunology, 2022, 11(1):2057012. doi: 10.1080/2162402X.2022.2057012
    [33] Pearson AD, Rossig C, MacKall C, et al. Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: accelerate in collaboration with the European Medicines Agency with participation of the Food and Drug Administration[J]. Eur J Cancer, 2022, 160:112-133. doi: 10.1016/j.ejca.2021.10.016
    [34] DuBois SG, Mosse YP, Fox E, et al. Phase II trial of alisertib in combination with irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma[J]. Clin Cancer Res, 2018, 24(24):6142-6149.
    [35] Moreno L, Barone G, DuBois SG, et al. accelerating drug development for neuroblastoma: summary of the second neuroblastoma drug development strategy forum from innovative therapies for children with cancer and International Society of Paediatric Oncology Europe Neuroblastoma[J]. Eur J Cancer, 2020, 136:52-68. doi: 10.1016/j.ejca.2020.05.010
    [36] Alleboina S, Aljouda N, Miller M, et al. Therapeutically targeting oncogenic CRCs facilitates induced differentiation of NB by RA and the BET bromodomain inhibitor[J]. Mol Ther Oncolytics, 2021, 23:181-191.
    [37] Chen JW, Nelson C, Wong M, et al. Targeted therapy of TERT-rearranged neuroblastoma with BET bromodomain inhibitor and proteasome inhibitor combination therapy[J]. Clin Cancer Res, 2021, 27(5):1438-1451. doi: 10.1158/1078-0432.CCR-20-3044
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  • 收稿日期:  2022-10-10
  • 录用日期:  2022-12-26
  • 修回日期:  2022-12-19