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The NCI-MATCH subprogram revealed key biomarkers of gemcitabine resistance through multi omics analysis (whole exome sequencing, RNA seq) (Yang et al., 2021): RRM2 gene amplification (copy number 4) significantly increased the risk of single drug resistance (HR = 2.1), dCK promoter hypermethylation led to drug activation disorders, and low infiltration of CD8 + T cells indicated immune microenvironment suppression (Carpenter et al., 2020)