Colorectal Cancer Puzzle: m6A Modification and Its Intricate Relationship With Drug Resistance

Colorectal cancer (CRC) is a globally prevalent malignancy with rising incidence and mortality rates over the past decades. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotes, and plays a pivotal role in post-transcriptional regulation. m6A is dynamically modulated by three core components, namely methyltransferases (writers), demethylases (erasers), and binding proteins (readers), which together govern the transcription, processing, translation, decay, and stability of mRNA. There has been accumulating evidence for the association of dysregulated m6A modification with CRC pathogenesis, metastasis, and therapeutic resistance. This review summarizes the biogenesis of m6A modification and its regulatory mechanisms, and discusses the dysregulation of m6A-related factors in CRC and the functional impacts. Most importantly, the review highlights the key roles of m6A modification in mediating CRC resistance to chemotherapy, targeted therapy, and immunotherapy. These insights may facilitate the development of novel therapeutic strategies for CRC.