AUTHOR=Liu Zhihui , Chen Samuel S. , Clarke Saki , Veschi Veronica , Thiele Carol J. 

TITLE=Targeting MYCN in Pediatric and Adult Cancers

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.623679

DOI=10.3389/fonc.2020.623679

ISSN=2234-943X

ABSTRACT=<p>The deregulation of the <italic>MYC</italic> family of oncogenes, including <italic>c-MYC</italic>, <italic>MYCN</italic> and <italic>MYCL</italic> occurs in many types of cancers, and is frequently associated with a poor prognosis. The majority of functional studies have focused on <italic>c-MYC</italic> due to its broad expression profile in human cancers. The existence of highly conserved functional domains between <italic>MYCN</italic> and <italic>c-MYC</italic> suggests that <italic>MYCN</italic> participates in similar activities. <italic>MYC</italic> encodes a basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (TF) whose central oncogenic role in many human cancers makes it a highly desirable therapeutic target. Historically, as a TF, MYC has been regarded as “undruggable”. Thus, recent efforts focus on investigating methods to indirectly target MYC to achieve anti-tumor effects. This review will primarily summarize the recent progress in understanding the function of <italic>MYCN</italic>. It will explore efforts at targeting <italic>MYCN</italic>, including strategies aimed at suppression of <italic>MYCN</italic> transcription, destabilization of MYCN protein, inhibition of <italic>MYCN</italic> transcriptional activity, repression of MYCN targets and utilization of <italic>MYCN</italic> overexpression dependent synthetic lethality.</p>