Neuroblastoma: Molecular Mechanisms and Novel Treatment Strategies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (20 March 2025) | Viewed by 466

Special Issue Editor


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Guest Editor
Histone Modification in Cancer, Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia
Interests: cancer therapy; histone modification enzymes; histone modification enzyme inhibitors; long noncoding RNA
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Special Issue Information

Dear Colleagues,

We are pleased to announce a Call for Papers for manuscripts on “Neuroblastoma: Molecular Mechanisms and Novel Treatment Strategies”. Neuroblastoma, a pediatric malignancy, continues to present significant challenges due to its complex genetic and epigenetic landscape, high-risk classifications, and poor survival outcomes in relapsed cases. Understanding the underlying molecular mechanisms is crucial for developing more effective and targeted therapies.

We invite original research articles and reviews that explore innovative approaches for understanding the biology of neuroblastoma and novel treatment strategies. Topics of interest include, but are not limited to, targeted therapies (e.g., against MYCN), immunotherapies, and epigenetic interventions. Studies focusing on drug resistance mechanisms, biomarkers for personalized medicine, and emerging treatment strategies are welcome.

This Special Issue encourages researchers to contribute high-quality manuscripts that advance our knowledge in the field and provide new insights for combating neuroblastoma. Submissions will undergo peer review to ensure scientific rigor and impact.

Prof. Dr. Tao Liu
Guest Editor

Manuscript Submission Information

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Keywords

  • neuroblastoma
  • tumorigenesis
  • biomarkers
  • drug discovery
  • experimental therapy

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Published Papers (1 paper)

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Research

15 pages, 1996 KB  
Article
PA2G4 Functions as a Cofactor for MYC Family Oncoproteins in MYC-Driven Malignancies
by Sukriti Krishan, Jessica Koach, Taylor Lim, Kenny Yeo, Faith Cheong, Jie-Si Luo, Hassina Massudi, Xiaomian Gao, Sopheakwealthy Heangsarath, Andrew J. Kueh, Marco J. Herold, Belamy B. Cheung and Glenn M. Marshall
Cells 2025, 14(18), 1422; https://doi.org/10.3390/cells14181422 - 11 Sep 2025
Viewed by 147
Abstract
MYCN and c-MYC are critical driver oncogenes in several childhood cancers, including neuroblastoma. Currently, the clinical development of MYC inhibitors has been hindered by the intrinsically disordered structure of MYC proteins, which lack well-defined ligand-binding pockets. Proliferation-associated protein 2G4 (PA2G4) directly binds to [...] Read more.
MYCN and c-MYC are critical driver oncogenes in several childhood cancers, including neuroblastoma. Currently, the clinical development of MYC inhibitors has been hindered by the intrinsically disordered structure of MYC proteins, which lack well-defined ligand-binding pockets. Proliferation-associated protein 2G4 (PA2G4) directly binds to and stabilizes MYCN protein, leading to markedly increased MYCN levels in neuroblastoma cells. Here, we demonstrate that PA2G4 is essential for MYCN-driven tumor growth in neuroblastoma in vivo. Moreover, PA2G4 elevates c-MYC protein levels in neuroblastoma cells by inhibiting its ubiquitin-mediated degradation. In turn, c-MYC upregulates the transcription and protein expression of PA2G4, creating an oncogenic feed-forward expression loop. A small molecule PA2G4 inhibitor, WS6, directly disrupts the PA2G4-c-MYC protein–protein interaction, resulting in decreased levels of both PA2G4 and c-MYC. WS6 exhibited selective cytotoxicity in c-MYC-overexpressing cell lines. Together, these findings identify PA2G4 as a shared cofactor for both the c-MYC and MYCN oncoproteins and highlight its interaction with MYC family oncoproteins as a promising therapeutic vulnerability in MYC-driven cancers. Full article
(This article belongs to the Special Issue Neuroblastoma: Molecular Mechanisms and Novel Treatment Strategies)
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