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神经母细胞瘤诊断、治疗与研究的新趋势

Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.

作者信息

Sharma Rishabh, Yadav Jaya, Bhat Sajad Ahmad, Musayev Abdugani, Myrzagulova Syrsulu, Sharma Deepika, Padha Nipun, Saini Manju, Tuli Hardeep Singh, Singh Tejveer

机构信息

Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India.

Amity Stem Cell Institute, Amity Medical School, Amity University, Haryana, 122412, India.

出版信息

Mol Neurobiol. 2025 May;62(5):6423-6466. doi: 10.1007/s12035-024-04680-w. Epub 2025 Jan 13.

Abstract

This review explores the current understanding and recent advancements in neuroblastoma, one of the most common extracranial solid pediatric cancers, accounting for ~ 15% of childhood cancer-related mortality. The hallmarks of NBL, including angiogenesis, metastasis, apoptosis resistance, cell cycle dysregulation, drug resistance, and responses to hypoxia and ROS, underscore its complex biology. The tumor microenvironment's significance in disease progression is acknowledged in this study, along with the pivotal role of cancer stem cells in sustaining tumor growth and heterogeneity. A number of molecular signatures are being studied in order to better understand the disease, with many of them serving as targets for the development of new therapeutics. This includes inhibitor therapies for NBL patients, which notably concentrate on ALK signaling, MDM2, PI3K/Akt/mTOR, Wnt, and RAS-MAPK pathways, along with regulators of epigenetic mechanisms. Additionally, this study offers an extensive understanding of the molecular therapies used, such as monoclonal antibodies and CAR-T therapy, focused on both preclinical and clinical studies. Radiation therapy's evolving role and the promise of stem cell transplantation-mediated interventions underscore the dynamic landscape of NBL treatment. This study has also emphasized the recent progress in the field of diagnosis, encompassing the adoption of artificial intelligence and liquid biopsy as a non-intrusive approach for early detection and ongoing monitoring of NBL. Furthermore, the integration of innovative treatment approaches such as CRISPR-Cas9, and cancer stem cell therapy has also been emphasized in this review.

摘要

本综述探讨了神经母细胞瘤(最常见的儿童颅外实体癌之一,约占儿童癌症相关死亡率的15%)的当前认识和最新进展。神经母细胞瘤的特征,包括血管生成、转移、抗凋亡、细胞周期失调、耐药性以及对缺氧和活性氧的反应,突出了其复杂的生物学特性。本研究承认肿瘤微环境在疾病进展中的重要性,以及癌症干细胞在维持肿瘤生长和异质性方面的关键作用。为了更好地理解这种疾病,正在研究许多分子特征,其中许多可作为开发新疗法的靶点。这包括针对神经母细胞瘤患者的抑制剂疗法,这些疗法特别集中于ALK信号传导、MDM2、PI3K/Akt/mTOR、Wnt和RAS-MAPK途径,以及表观遗传机制的调节因子。此外,本研究还对所使用的分子疗法,如单克隆抗体和CAR-T疗法,进行了广泛的阐述,重点涉及临床前和临床研究。放射治疗不断演变的作用以及干细胞移植介导的干预措施的前景突出了神经母细胞瘤治疗的动态格局。本研究还强调了诊断领域的最新进展,包括采用人工智能和液体活检作为一种非侵入性方法用于神经母细胞瘤的早期检测和持续监测。此外,本综述还强调了CRISPR-Cas9等创新治疗方法以及癌症干细胞疗法的整合。

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