Am J Cancer Res 2012;2(4):383-396
Review Article
Autophagy in pancreatic cancer pathogenesis and treatment
Rui Kang, Daolin Tang
Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15219, USA
Received May 1, 2012; accepted May 23, 2012; Epub June 28, 2012; Published July 15, 2012
Abstract: Pancreatic cancer is the fourth most common cancer to cause death due to advanced stage at diagnosis and poor
response to current treatment. Autophagy is the lysosome-mediated degradation pathway which plays a critical role in cellular
defense, quality control, and energy metabolism. Targeting autophagy is now an exciting field for translational cancer research,
as autophagy dysfunction is among the hallmarks of cancer. Pancreatic tumors have elevated autophagy under basal conditions
when compared with other epithelial cancers. This review describes our current understanding of the interaction between
autophagy and pancreatic cancer development, including risk factors (e.g., pancreatitis, smoking, and alcohol use), tumor
microenvironment (e.g., hypoxia and stromal cells), and molecular biology (e.g., K-Ras and p53) of pancreatic cancer. The
importance of the HMGB1-RAGE pathway in regulation of autophagy and pancreatic cancer is also presented. Finally, we
describe current studies involving autophagy inhibition using either pharmacological inhibitors (e.g., chloroquine) or RNA
interference of essential autophagy genes that regulate chemotherapy sensitivity in pancreatic cancer. Summarily, autophagy
plays multiple roles in the regulation of pancreatic cancer pathogenesis and treatment, although the exact mechanisms remain
unknown. (AJCR0000119)
Kewords: Autophagy, pancreatic cancer, oncogene, hypoxia, pancreatitis, HMGB1, RAGE, p53, HIF1α, AMPK
Address all correspondence to:
Dr. Daolin Tang
Department of Surgery
Hillman Cancer Center
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania 15219, USA.
E-mail: tangd2@upmc.edu
Review Article
Autophagy in pancreatic cancer pathogenesis and treatment
Rui Kang, Daolin Tang
Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15219, USA
Received May 1, 2012; accepted May 23, 2012; Epub June 28, 2012; Published July 15, 2012
Abstract: Pancreatic cancer is the fourth most common cancer to cause death due to advanced stage at diagnosis and poor
response to current treatment. Autophagy is the lysosome-mediated degradation pathway which plays a critical role in cellular
defense, quality control, and energy metabolism. Targeting autophagy is now an exciting field for translational cancer research,
as autophagy dysfunction is among the hallmarks of cancer. Pancreatic tumors have elevated autophagy under basal conditions
when compared with other epithelial cancers. This review describes our current understanding of the interaction between
autophagy and pancreatic cancer development, including risk factors (e.g., pancreatitis, smoking, and alcohol use), tumor
microenvironment (e.g., hypoxia and stromal cells), and molecular biology (e.g., K-Ras and p53) of pancreatic cancer. The
importance of the HMGB1-RAGE pathway in regulation of autophagy and pancreatic cancer is also presented. Finally, we
describe current studies involving autophagy inhibition using either pharmacological inhibitors (e.g., chloroquine) or RNA
interference of essential autophagy genes that regulate chemotherapy sensitivity in pancreatic cancer. Summarily, autophagy
plays multiple roles in the regulation of pancreatic cancer pathogenesis and treatment, although the exact mechanisms remain
unknown. (AJCR0000119)
Kewords: Autophagy, pancreatic cancer, oncogene, hypoxia, pancreatitis, HMGB1, RAGE, p53, HIF1α, AMPK
Address all correspondence to:
Dr. Daolin Tang
Department of Surgery
Hillman Cancer Center
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania 15219, USA.
E-mail: tangd2@upmc.edu
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American Journal of Cancer Research
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