N6-methyladenosine (m6A) modifications are among the most prevalent epigenetic marks in eukaryotic RNAs, regulating both coding and non-coding RNAs and playing a pivotal role in RNA metabolism. Given their widespread influence, m6A modifications are deeply implicated in the pathogenesis of various cancers, including highly aggressive malignancies such as lung cancer, melanoma, and liver cancer. Dysregulation of m6A dynamics—marked by an imbalance in methylation and demethylation—can drive tumor progression, enhance metastatic potential, increase aggressiveness, and promote drug resistance, while also exerting context-dependent tumor-suppressive effects. Given this dual role, precise modulation of m6A levels and the activity of its regulatory enzymes (writers, erasers, and readers) represent a promising therapeutic avenue. In this review, we highlight recent advances in targeting m6A machinery, including small-molecule inhibitors, antisense oligonucleotides, and CRISPR/Cas-based editing tools, capable of both writing and erasing m6A marks and altering m6A methylation sites per se. By evaluating these strategies, we aim to identify the most effective approaches for restoring physiological m6A homeostasis or for strategically manipulating the m6A machinery for therapeutic benefit.
Shpiliukova et al. (Wed,) studied this question.