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Epigenetic regulation of drug resistance In the epigenetic regulatory network of gemcitabine resistance, long noncoding RNA (lncRNA) mediated RRM2 regulation and dynamic regulation of drug-metabolizing enzymes by m 6 A (N6-methyladenosine) methylation modification are two key mechanisms that together constitute a complex resistance network: In the mechanism of gemcitabine resistance, oncogenic lncRNAs (such as MALAT1 and NEAT1) significantly promote the expression of ribonucleotide reductase M2 (RRM2) through epigenetic regulation (Wang et al., 2021)

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For example, some patients may exhibit more prominent mitochondrial respiratory chain abnormalities and metabolic reprogramming