title: Molecularly targeted therapies in metastatic pancreatic cancer: a systematic review.
abstract: Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable.
authors.affiliation: Comprehensive Cancer Center Vienna, Department of Medicine I, Medical University of Vienna, Vienna, Austria. florazagouri@yahoo.co.uk
authors.forename: Flora
authors.initials: F
authors.lastname: Zagouri
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Sergentanis
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Chrysikos
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Zografos
authors.forename: Christos A
authors.initials: CA
authors.lastname: Papadimitriou
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
mesh_terms: D000970:Antineoplastic Agents / Q000145:classification / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors