Crosstalk between lactylation and m6A in cancer: emerging disease mechanisms and therapeutic targets.

Protein post-translational modifications (PTMs) and RNA modifications represent cutting-edge frontiers in cancer research. As a novel PTM, lactylation has been extensively implicated in tumor progression. Meanwhile, N6-methyladenosine (m6A), the most prevalent RNA modification, dictates cancer cell fate by governing RNA. Both modifications play pivotal roles in cancer initiation and progression, metabolic reprogramming, immune microenvironment remodeling, and therapeutic resistance. Accumulating evidence has revealed extensive and intricate functional crosstalk between lactylation and m6A, serving as a central bridge linking tumor metabolic reprogramming and epigenetic transcriptional regulation, and offering a novel perspective for elucidating cancer pathogenesis. This review provides an in-depth dissection of the crosstalk mechanisms between lactylation and m6A, highlighting their implications for targeted cancer therapy. Combination therapeutic strategies based on these mechanisms exhibit promising clinical translational potential.