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Response of Pancreatic Cancer Cell Lines to the Polyamine Analog, PG-11047

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a deadly malignancy (1). While the etiology of this specific cancer type is not well known, it has been suspected that polyamine dysregulation may play a critical role in the proliferation of cancer cells (2). Polyamines are organic compounds that promote normal cell growth and survival, yet the dysfunction of their inherent regulatory controls has been identified as a recurrent component of several cancers (2). Here, we examine the effects of PG-11047, a drug targeted to interfere with polyamine regulation, on several PDA cell lines. Following exposure to PG-11047, 72-hour cancer cell growth inhibition was determined to produce a drug dose response curve. The PDA cell lines showed a variable range of response to PG-11047, with certain cell lines being sensitive to the drug and others being resistant. Genome-wide mRNA expression profiles of the cancer cell line were supervised with drug sensitivity data to discover molecular correlates of drug response. These variable responses indicate that certain cancer subtypes may proliferate due to polyamine dysregulation while the resistant cancer subtypes do not. These results have importance for the personalization of cancer therapy in PDA.

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