Repurposing metformin, simvastatin and digoxin as a combination for targeted therapy for pancreatic ductal adenocarcinoma

Cancer Lett. 2020 Oct 28:491:97-107. doi: 10.1016/j.canlet.2020.08.002. Epub 2020 Aug 21.


Patients with pancreatic adenocarcinoma (PDAC) have a 5-year survival rate of 8%, the lowest of any cancer in the United States. Traditional chemotherapeutic regimens, such as gemcitabine- and fluorouracil-based regimens, often only prolong survival by months. Effective precision targeted therapy is therefore urgently needed to substantially improve survival. In an effort to expedite approval and delivery of targeted therapy to patients, we utilized a platform to develop a novel combination of FDA approved drugs that would target pancreaticoduodenal homeobox1 (PDX1) and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) utilizing super-promoters of the target genes to interrogate an FDA approved drug library. We identified and selected metformin, simvastatin and digoxin (C3) as a novel combination of FDA approved drugs, which were shown to effectively target PDX1 and BIRC5 in human PDAC tumors in mice with no toxicity.

Keywords: BIRC5; FDA Approved drug libraries; High throughput screening; PDX1; Super promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Digoxin / administration & dosage*
  • Drug Combinations
  • Drug Repositioning*
  • Drug Synergism
  • High-Throughput Screening Assays
  • Homeodomain Proteins / antagonists & inhibitors*
  • Humans
  • Male
  • Metformin / administration & dosage*
  • Mice
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Simvastatin / administration & dosage*
  • Survivin / antagonists & inhibitors*
  • Trans-Activators / antagonists & inhibitors*


  • Drug Combinations
  • Homeodomain Proteins
  • Survivin
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Digoxin
  • Metformin
  • Simvastatin