title: Advanced or metastatic pancreatic cancer: molecular targeted therapies.
abstract: Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. However, clinical developments over the past decade have been modest and advances are incremental at most. The core drug and the backbone of treatment in all settings of pancreatic adenocarcinoma-adjuvant, locally advanced, and metastatic-remains gemcitabine. The past decade of research focused initially on combining cytotoxic therapies with gemcitabine, and during that time a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis, and resistance to apoptosis. This research is of particular importance, as data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis. Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated marginal survival benefit in combination with gemcitabine in phase III clinical trials. Even though the failures of targeted therapies in the clinical setting are discouraging, it is reasonable to surmise that major progress will evolve as the molecular biology of pancreatic adenocarcinoma continues to be unraveled. This review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.
authors.affiliation: Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, University of Miami, Miami, FL, USA.
authors.forename: Soley
authors.initials: S
authors.lastname: Bayraktar
authors.forename: Caio M
authors.initials: CM
authors.lastname: Rocha-Lima
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D011506:Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A
chemical_list: D000911:Antibodies, Monoclonal; D052246:Cyclooxygenase 2 Inhibitors; C121623:PSMF1 protein, human; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D045726:Metalloproteases; D046988:Proteasome Endopeptidase Complex