title: Metformin and pancreatic cancer: Is there a role?
abstract: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA, with a 5-year survival rate of 6 %. Anti-hyperglycemic treatments for type 2 diabetes mellitus that induce hyperinsulinemia (i.e., sulfonylureas) are thought to increase cancer risk, whereas treatments that lower insulin resistance and hyperinsulinemia (i.e., metformin) are considered cancer prevention strategies. Metformin is a cornerstone in the treatment of diabetes mellitus type 2. Retrospective studies have shown a survival benefit in diabetic patients with many solid tumors including pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Ongoing research is redefining our understanding about how metformin modulates the molecular pathways implicated in pancreatic cancer. The authors review the topic critically and also give their opinion. Further studies investigating the effect of metformin in combination with chemotherapy, targeted agents, or radiation therapy are undergoing. In addition, the role of metabolic and other biomarkers is needed.
authors.affiliation: Section of GI Cancers and Experimental Therapeutics, Department of Hematology and Oncology, Tufts University School of Medicine and Tufts Cancer Center, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: De Souza
authors.affiliation: Department of Endocrinology and Metabolism, Services Institute of Medical Sciences, Lahore, Pakistan.
authors.forename: Khadija Irfan
authors.initials: KI
authors.lastname: Khawaja
authors.affiliation: King Edward Medical University, Lahore, Pakistan.
authors.forename: Faisal
authors.initials: F
authors.lastname: Masud
authors.affiliation: Section of GI Cancers and Experimental Therapeutics, Department of Hematology and Oncology, Tufts University School of Medicine and Tufts Cancer Center, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA. wsaif@tuftsmedicalcenter.org.
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced / Q000150:complications; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008687:Metformin / Q000378:metabolism / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013453:Sulfonylurea Compounds / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: Hyperinsulinemia; Pancreatic neoplasms; Prognosis; Type 2 diabetes mellitus