Next, to investigate the role of the RRM2-let-7 interplay on acquired gemcitabine chemoresistance, we first chronically treated gemcitabine-sensitive human pancreatic cancer cell lines (L3.6pl and Capan-1) [23] with escalating doses of gemcitabine (5–20 nM), and surviving clones with characteristics of acquired gemcitabine resistance were investigated. This evidence concerns the gene RRM2 and pancreatic neoplasm.