title: Metformin in pancreatic cancer treatment: from clinical trials through basic research to biomarker quantification.
abstract: OBJECTIVE
  Three major chemotherapy strategies have emerged in the treatment of PDAC in the recent past: multiple drug combination, stroma depletion, and use of nanodrug therapy. Anti-diabetic metformin was shown to improve the outcome of a number of cancer types the first seminal report on an observational study published in 2005 and the first hospital-based case-control study on pancreatic cancer in 2009.
  
  
  METHODS
  In this review paper, we confront the findings of a selected number of epidemiological studies and clinical trials on the use of metformin in pancreatic cancer treatment with basic knowledge and research. We particularly emphasize on the point that contradictory clinical results likely originate from heterogeneous study design due to a trial and error approach rather than an evidence-based and scientific approach. A non-rigorous selection of patients suffering from PDAC and often a poor understanding of the biological mechanism of metformin coupled with lack of scientific data has led to general statements on metformin positive or negative action, another aspect which we highlight in the review.
  
  
  RESULTS
  We here present a few pathways which in our opinion are predominant for pancreatic cancer specifically: mitochondrial activity, AMPK activation, mTOR inhibition, and decreased IGF-1R and HIF-1α expression.
  
  
  CONCLUSIONS
  We stress on the need for a better stratification of patients and a more rigorous planning of clinical trials not only focusing on classical parameters but also on potential predictive biomarkers (AMPK, mTOR, HIF-1α, IGF-1R) and metformin dosage for positive outcome.
authors.affiliation: Centre for Biomedical and Biomaterials Research (CBBR), University of Mauritius, MSIRI Building, Réduit, Mauritius.
authors.forename: Archana
authors.initials: A
authors.lastname: Bhaw-Luximon
authors.affiliation: Centre for Biomedical and Biomaterials Research (CBBR), University of Mauritius, MSIRI Building, Réduit, Mauritius. dhanjayjhurry@gmail.com.
authors.forename: Dhanjay
authors.initials: D
authors.lastname: Jhurry
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic
chemical_list: D014408:Biomarkers, Tumor; D008687:Metformin
keywords: Biomarkers; Cancer biology; Clinical trials; Metformin; Pancreatic cancer