Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m⁶A (N6-methyladenosine). m⁶A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m¹A), 5-methylcytosine (m⁵C), 3-methylcytosine (m³C), pseudouridine (Ψ) and N7-methylguanosine (m⁷G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m⁶A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.