m⁶A RNA Modification: Technologies Behind Future Anti-Cancer Therapy

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.