Review

Tumor Biology

, Volume 35, Issue 6, pp 5101-5110

Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery

  • Mihaela AldeaAffiliated withResearch Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Email author 
  • , Lucian CraciunAffiliated withResearch Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Email author 
  • , Ciprian TomuleasaAffiliated withResearch Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and PharmacyDepartment of Hematology, Ion Chiricuta Comprehensive Cancer Center in Cluj Napoca, Romania
  • , Ioana Berindan-NeagoeAffiliated withResearch Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and PharmacyDepartment of Genetics, Ion Chiricuta Comprehensive Cancer Center in Cluj Napoca, Romania
  • , Gabriel KacsoAffiliated withDepartment of Medical Oncology and Radiotherapy, Iuliu Hatieganu University of Medicine and Pharmacy
  • , Ioan Stefan FlorianAffiliated withDepartment of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy
  • , Carmen CriviiAffiliated withDepartment of Morphological Sciences, Iuliu Hatieganu University of Medicine and Pharmacy

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Abstract

After sitting many years on the shelves of drug stores as a harmless antidiabetic drug, metformin comes back in the spotlight of the scientific community as a surprisingly effective antineoplastic drug. Metformin targets multiple pathways that play pivotal roles in cancer progression, impacting various cellular processes, such as proliferation, cell death, metabolism, and even the cancer stemness features. The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin’s anticancer efficiency. This could indicate a need for tumor genetic profiling in order to identify patients most likely to benefit from metformin treatment. Considering that the majority of experimental models suggest that higher, supra-clinical doses of metformin should be used in order to obtain an antineoplastic effect, new ways of drug delivery could be developed, such as metformin-loaded nanoparticles or incorporation of metformin into microparticles used in transarterial chemoembolization, with the aim of obtaining higher intratumoral drug concentrations and a targeted therapy which will ultimately maximize metformin’s efficacy.

Keywords

Cancer Metformin Stem Genetic Nanoparticle Chemoembolization