Targeting MyCN and MDM2 offers new hope for cancer therapy

Targeting MyCN and MDM2 offers new hope for cancer therapy

Over the last two decades, the idea of ​​targeting transcription factors to combat malignancies has transformed into a clinical reality. Targeting oncogenes and their interactive partners is a powerful approach to developing new targeted therapies for cancer and other chronic diseases. The Myc family of proteins, which are transcription factors, play central roles 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 studied oncogenes and an excellent target for cancer therapy based on its p53-dependent and p53-independent oncogenic activities in various cancer types.

This comprehensive review was published in theGenes and diseasesJournal by a team from the Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy and Drug Discovery Institute, the University of Houston focuses on the oncogenic properties of MyCN and their molecular regulation and encapsulates the key therapeutic strategies being developed based on the preclinical findings based on the present findings. This review also highlights the potential benefits of targeting both MyCN and MDM2 oncogenes and provides preclinical evidence for 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 studies provide evidence that inhibiting MDM2 could be a potential therapeutic approach for neuroblastoma. Furthermore, the concept of dual inhibition, which effectively restricts 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 inhibits both MyCN-mediated tumorigenesis and MDM2-regulated survival of neuroblastoma cells. MyCN and MDM2 inhibition has received attention due to their potential in targeting key oncogenic pathways not only in neuroblastoma but also in a spectrum of other cancer types. Therefore, exploring synergistic combination therapies that include targeted agents, immunotherapies, and conventional treatments remains of paramount importance in achieving maximum therapeutic results while reducing resistance.

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

Sources: