AUTHOR=Zhang Honghai , Wang Xueer , Chen Jianjun , Su Rui 

TITLE=Combating cancer stem cells: RNA m6A methylation and small-molecule drug discovery

JOURNAL=Frontiers in Drug Discovery

VOLUME=4

YEAR=2024

URL=https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2024.1465222

DOI=10.3389/fddsv.2024.1465222

ISSN=2674-0338

ABSTRACT=<p>Cancer stem cells (CSCs) are a small population of less differentiated cells with robust self-renewal ability. CSCs have been recognized as the root cause of tumor initiation, progression, relapse, and drug resistance. Recent studies from us and others have highlighted that <italic>N</italic><sup>6</sup>-methyladenosine (m<sup>6</sup>A), the most prevalent modification in mRNA, plays a crucial role in carcinogenesis and CSC homeostasis. Dysregulation of the m<sup>6</sup>A modification machinery has been implicated in CSC survival and self-renewal, thereby regulating cancer progression and therapeutic resistance. In this review, we provide an overview of the roles and molecular mechanisms of the RNA m<sup>6</sup>A modification machinery in CSC survival and self-renewal. Additionally, we summarize the currently known small-molecule inhibitors targeting the dysregulated m<sup>6</sup>A modification machinery and discuss proof-of-concept studies focusing on the efficacy of these compounds in eliminating CSCs and cancers.</p>