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Targeting MYCN in Pediatric and Adult Cancers

Zhihui Liu1, Samuel S Chen1, Saki Clarke1

  • 1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.

Frontiers in Oncology
|February 25, 2021
PubMed

Insights

MYCN oncogene deregulation drives cancer progression and poor prognosis. This review highlights MYCN functions and explores novel therapeutic strategies targeting MYCN's transcriptional activity and downstream effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The MYC oncogene family, including c-MYC, MYCN, and MYCL, is frequently deregulated in various cancers, correlating with poor patient outcomes.
  • While c-MYC has been extensively studied, MYCN's conserved functional domains suggest similar oncogenic roles, necessitating focused research.
  • MYC proteins function as transcription factors (TFs) and are recognized as critical therapeutic targets, though historically considered

Purpose of the Study:

  • To review recent advancements in understanding the biological functions of the MYCN oncogene.
  • To explore emerging therapeutic strategies targeting MYCN in cancer treatment.
  • To consolidate knowledge on indirect targeting approaches for MYC family oncogenes.

Main Methods:

  • Literature review of functional studies on MYCN.
  • Analysis of therapeutic strategies targeting MYCN transcription, protein stability, and activity.
  • Examination of approaches involving repression of MYCN targets and synthetic lethality.

Main Results:

  • MYCN plays a significant role in oncogenesis, similar to c-MYC, due to conserved functional domains.
  • Various indirect therapeutic strategies are being developed to target MYCN.
  • These strategies include suppressing MYCN transcription, destabilizing MYCN protein, inhibiting its transcriptional activity, and exploiting synthetic lethality.

Conclusions:

  • MYCN is a crucial oncogene with significant therapeutic potential.
  • Developing effective MYCN-targeting therapies is essential for improving cancer treatment outcomes.
  • Further research into MYCN's function and druggability will pave the way for novel anti-cancer treatments.
Keywords:
MYCMYCNSuper-enhancer (SE)cancercofactorpediatric cancertranscription factor

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