Targeted agents in the treatment of pancreatic cancer: history and lessons learned.
OBJECTIVE
The treatment of pancreatic cancer is an ongoing challenge with minimal substantive improvement in patient outcomes despite many randomized phase III clinical trials evaluating multiple agents, both alone and in combination. Such disappointing outcomes clearly call for broadening the scope of pharmacologic approaches to managing this disease. With increasing insight into pathways within tumor cells that are related to tumor growth and spread, and development of 'targeted therapies' against these pathways, much attention has turned to the use of these agents, alone or coupled with chemotherapy, in the treatment of pancreatic cancer.


RESULTS
Several targeted agents have been studied in patients with pancreatic cancer. Of the agents studied, the only agent that has shown to provide a modest but significant benefit in survival for these patients is erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.


CONCLUSIONS
From trials done to date, minimal benefit has been found with the addition of targeted agents in the treatment of pancreatic cancer. More potential pathways remain to be targeted, however, and there are a plethora of new agents to be tested. Due to the likelihood that different pathways drive the development and growth of different tumors of the same site of origin the inclusion of biomarker studies to correlate with treatment effect may be a necessary component of clinical trials to learn how to best tailor therapy to the patient.
Bendell
Johanna
J
Duke University Medical Center, North Carolina, USA.
Goldberg
Richard M
RM
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D061965:Matrix Metalloproteinase Inhibitors; D051231:Farnesyltranstransferase; D066246:ErbB Receptors