Targeted therapies for pancreatic adenocarcinoma.
The majority of patients diagnosed with adenocarcinoma of the pancreas have advanced disease at presentation, with only 20% surviving beyond one year. Even among the 10% to 15% of patients who present with localized disease, only 20% will be alive 5 years post surgical resection. Systemic therapy for pancreatic adenocarcinoma to date has failed to provide more than a very modest survival benefit for patients with advanced disease. However, the past decade has seen significant advances in the understanding of the molecular pathogenesis of pancreatic cancer, culminating in the sequencing of the pancreatic cancer genome. New generations of therapeutic agents targeting key oncogenic cellular signaling pathways are currently under evaluation in advanced pancreatic adenocarcinoma. Although thus far only erlotinib has been shown to improve survival when compared to gemcitabine monotherapy, the authors anticipate that further developments in biomarker analysis and pharmacogenomics, along with the identification of new drugs will help maximize the benefit of novel therapeutics by directing effective use in the future. Herein the authors review the evidence to date for the use of novel cytotoxic and molecularly targeted agents in pancreatic adenocarcinoma, and discuss key areas for future therapeutic development.
Memorial Sloan-Kettering Cancer Centre, Weill Medical College of Cornell University, Department of Medicine, GI Oncology ServiceNew York, NY, USA. lowerym@mskcc.org
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D000230:Adenocarcinoma / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D018631:ras Proteins / Q000037:antagonists & inhibitors*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D017479:Receptors, Platelet-Derived Growth Factor; D019061:src-Family Kinases; D018631:ras Proteins