ARTICLE Modulation of Pancreatic Cancer Chemoresistance by Inhibition

Pancreatic adenocarcinoma is one of the most lethal and poorly understood human malignancies. Because of the lack of effective systemic therapies, the 5-year survival rate for patients with pan-creatic adenocarcinoma has remained at 1%–3%, without change over the past 25 years (1). Hence, development of novel chemo-therapeutic approaches that reduce the intrinsic drug resistance of this disease poses one of the greatest challenges in pancreatic cancer research. Nuclear factor kB (NF-kB) and activator protein-1 (AP-1) are key transcriptional factors that orchestrate expression of many genes involved in inflammation, oncogenesis, and apoptosis (2,3). NF-kB is constitutively activated in numerous hematologic malig-nancies and solid tumors (4–7), including pancreatic cancer (8), and its activation can suppress proapoptotic signaling pathways through the expression of several antiapoptotic genes (5). The exact func-tion of AP-1 in cellular responses to genotoxic stress has not bee