In this review, we give an overview of the actual role of proteomic technologies in the study of
pancreatic cancers (PCs). We describe PC proteomics on the basis of sample origins, i.e.
tissues, body fluids, and PC cell lines. As regards PC tissues, we report the identification of a
number of candidate biomarkers of precursor lesions that may allow early diagnosis of this
neoplasia. Moreover, we describe cytoskeletal and hypoxia-regulated proteins that confirm the
involvement of cytoskeleton modifications and metabolism adaptations in carcinogenesis. We
also discuss the most important biomarkers identified by proteomic analysis involved in local
invasion and distant metastasis, and in the cross-talk between pancreatic tumor and the
surrounding stroma. Furthermore, we report novel candidate biomarkers identified in serum,
plasma, and pancreatic juice of cancer patients compared with cancer-free controls. Proteomic
alterations in PC cell line models as compared to normal controls and studies on cell
lines treated with drugs or new agents to understand their mechanism of pharmacological
action or the onset of drug resistance are also presented. Finally, we discuss the recent
improvements obtained in classical 2-DE and high-throughput proteomic strategies able to
allow the overcoming of relevant proteomic drawbacks.