Recent investigation has also found overexpression of pancreatic adenocarcinoma up-regulated factor (PAUF) in CD44 + CD24 + ESA + PCSCs that attributes to both GEM and 5-FU resistance by increasing the mRNA expression of ATP-dependent multidrug-resistant protein 5 (MRP5, ABCC5) and ribonucleotide reductase regulatory subunit M2 (RRM2) [82]. Here, RRM2 is linked to pancreatic adenocarcinoma.