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Exanetide and Pancreatic Cancer: A Case Report and Review of Relevant Literature

Timothy L Cannon, Melany B Atkins, John F Deeken, Haresh Mani, Svetlana Rassulova, Megan Kokon, Donald L Trump

Abstract


Introduction: Pancreatic cancer is the 4th most common cause of cancer death in the United States, and is associated with a 5 year survival rate of 5%. In recent years, epidemiological studies have raised the concern about a link between the use of antidiabetic drugs that act along the glucagon-like peptide pathway and the development of pancreatic cancer.  Additionally, pre-clinical studies have suggested that GLP-1 pathway agents may promote the malignant progression of pancreatic intraepithelial (PanIN). Exenatide, which is a glucagon-like peptide -1 agonist (GLP-1), is among the most commonly used agents in this class. 

Case presentation: The patient described in this case report presented with stage IV pancreatic cancer 5 years after the initiation of exanetide.  The patient and her husband raised the question of an association between exanetide and her cancer. Unfortunately, her cancer was refractory to gemcitabine based therapy, and she succumbed to her disease shortly after diagnosis.

Conclusion:There is limited evidence to establish a link between this class of antidiabetic medication and pancreatic cancer. While there are preclinical studies that demonstrate a mechanism by which GLP-1 pathway drugs cause chronic pancreatitis and promotion of pancreatic oncogenesis, epidemiological studies are conflicting.  However, most of these studies had a fairly brief follow up period (< 5 years), and the process of oncogenesisis likely to be protracted over several years. This case, occurring 5 years after the initiation of the agent, highlights the need for longer epidemiological studies. As of 2007, over 700,000 patients had already used exanetide. Given the high usage of these medications and the poor prognosis associated with pancreatic cancer, any association is important. Long term clinical studies, and preclinical studies that explore the question of associated deleterious somatic mutations in this population are indicated.


Keywords


pancreatic cancer; diabetes; glucagon-like peptide-1 agonists; GLP-1;PanIn (PanIN); intraepithelial neoplasia

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References


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