title: Molecular and genetic bases of pancreatic cancer.
abstract: Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.
authors.affiliation: Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Vanja
authors.initials: V
authors.lastname: Vaccaro
authors.forename: Alain
authors.initials: A
authors.lastname: Gelibter
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Iapicca
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Modugno
authors.forename: Maria Simona
authors.initials: MS
authors.lastname: Pino
authors.forename: Carmen
authors.initials: C
authors.lastname: Nuzzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.forename: Paola
authors.initials: P
authors.lastname: Nistico
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D017720:Molecular Epidemiology; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D040901:Proteomics / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors