title: Diabetes, pancreatic cancer, and metformin therapy.
abstract: Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1), and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Department of Medicine, Veterans Affairs Los Angeles, CA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Department of Medicine, Veterans Affairs Los Angeles, CA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Robbins
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Department of Medicine, Veterans Affairs Los Angeles, CA, USA.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Lugea
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Department of Medicine, Veterans Affairs Los Angeles, CA, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Waldron
authors.affiliation: Cancer Prevention and Genetics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center Los Angeles, CA, USA.
authors.forename: Christie Y
authors.initials: CY
authors.lastname: Jeon
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center Los Angeles, CA, USA ; Department of Medicine, Veterans Affairs Los Angeles, CA, USA ; Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles Los Angeles, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pandol
keywords: AMPK; IGF-1; diabetes; insulin; mTOR; metformin; pancreatic cancer