REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1683331
This article is part of the Research TopicAdvancing MYC Targeting Strategies in Cancer TreatmentView all articles
Molecular Regulation and Therapeutic Targeting of MYCN in Neuroblastoma: A Comprehensive Review
Provisionally accepted
- 1Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
- 2Department of Ophthalmology and Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
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MYCN amplification defines a highly aggressive subtype of neuroblastoma and is strongly associated with poor clinical outcomes. Due to the intrinsically disordered structure of the N-Myc protein, it remains largely undruggable. This review provides a comprehensive summary of the molecular regulatory network surrounding MYCN, including upstream pathways, key cofactors, and downstream effectors involved in cell cycle control, metabolic reprogramming, and ferroptosis. We further discuss the roles of epigenetic modulators, noncoding RNAs, and positive feedback loops in sustaining MYCN-driven oncogenic programs. Emerging therapeutic strategies such as PROTACs, metabolic inhibitors, immune-based approaches, and RNA-targeting technologies offer promising alternatives to direct MYCN inhibition. This review aims to provide a theoretical foundation for future development of precise and effective therapies targeting MYCN-amplified neuroblastoma.
Keywords: MYCN amplification, N-myc, MYCN protein, Neuroblastoma, Epigenetic regulation, Protac, noncoding RNA, metabolic reprogramming
Received: 10 Aug 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Chen, Yang, Xiao, Yan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Naihong Yan, yannaihong@wchscu.cn
Ming Zhang, mingzhangscu@163.com
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