MYCN and MDM2: A Transformative Strategy in Cancer Therapy

CHONGQING , CHONGQING , CHINA, January 29, 2025 /EINPresswire.com/ -- Over the past two decades, the idea of targeting transcription factors to combat malignancies has turned into a clinical reality. Targeting oncogenes and their interactive partners is an effective approach to developing novel targeted therapies for cancer and other chronic diseases. The MYC family of proteins, which are transcription factors, play a pivotal role in many cellular processes. However, dysregulation of MYC, such as amplification of MYCN, is associated with tumorigenesis, especially for neuroblastoma. MDM2, on the other hand, is one of the most frequently studied oncogenes and is an excellent target for cancer therapy, based on its p53-dependent and p53-independent oncogenic activities in various cancers.

This comprehensive review published in the Genes & Diseases journal by a team from the Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, and Drug Discovery Institute, University of Houston focuses on the oncogenic properties of MYCN and its molecular regulation and encapsulates the major therapeutic strategies being developed based on preclinical findings. This review also highlights the potential benefits of targeting both the MYCN and MDM2 oncogenes, providing preclinical evidence of the efficacy and safety of this approach.

As a key survival signaling pathway, the MDM2/p53 axis is widely involved in the development of many tumors. Preclinical and clinical trials provide evidence to support the notion that inhibition of MDM2 could be a potential therapeutic approach for neuroblastoma. Furthermore, the concept of dual-targeted inhibition, which effectively restrains both MYCN and MDM2, along with other critical molecules in neuroblastoma progression, presents an intriguing strategy. Since there is a positive feedback loop between MYCN and MDM2, targeting MDM2 would inhibit both MYCN-mediated tumorigenesis and MDM2-regulated survival of neuroblastoma cells. MYCN and MDM2 inhibition has gained attention not only in neuroblastoma but also in a spectrum of other cancer types due to their potential in targeting key oncogenic pathways. Thus, the exploration of synergistic combination therapies, encompassing targeted agents, immunotherapies, and conventional treatments, remains paramount in achieving maximal therapeutic outcomes while minimizing resistance.

The authors emphasize that with continued research, innovative strategies, and a commitment to addressing the complexities of cancer biology, the future holds the promise of transformative breakthroughs in cancer therapy. In conclusion, the development of effective small molecules that inhibit both MYCN and MDM2 represents a promising new strategy for the treatment of neuroblastoma and other cancers.

Reference
Title of Original Paper Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?

DOI https://doi.org/10.1016/j.gendis.2023.101156

Journal Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

Funding Information:
National Institutes of Health (NIH)/National Cancer Institute (No. R01CA214019).
Additional partial support was provided by NCI grant R01CA240447.
Drug Discovery Institute Seeds Grant.

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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