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

Tumor Biology volume 35, pages 5101–5110 (2014)Cite this article

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.

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Acknowledgments

This research was financially supported by a research grant of the Iuliu Hatieganu University of Medicine and Pharmacy, offered to Mihaela Aldea, in accordance to contract 22714/38/06.10.2011, and by the POSCCE 709/2010 (BREASTIMPACT) research grant.

Conflicts of interest

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Affiliations

  1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Str, Cluj-Napoca, 400337, Romania

    Mihaela Aldea, Lucian Craciun, Ciprian Tomuleasa & Ioana Berindan-Neagoe

  2. Department of Hematology, Ion Chiricuta Comprehensive Cancer Center in Cluj Napoca, Romania, 23 Marinescu Str, Cluj-Napoca, 400337, Romania

    Ciprian Tomuleasa

  3. Department of Genetics, Ion Chiricuta Comprehensive Cancer Center in Cluj Napoca, Romania, 23 Marinescu Str, Cluj-Napoca, 400337, Romania

    Ioana Berindan-Neagoe

  4. Department of Medical Oncology and Radiotherapy, Iuliu Hatieganu University of Medicine and Pharmacy, 34-36 Republicii Str, Cluj Napoca, 400015, Romania

    Gabriel Kacso

  5. Department of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, 34-36 Republicii Str, Cluj Napoca, 400015, Romania

    Ioan Stefan Florian

  6. Department of Morphological Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, 3-5 Clinicilor Street, Cluj-Napoca, Cluj, 400337, Romania

    Carmen Crivii

Authors
  1. Mihaela Aldea
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  2. Lucian Craciun
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  3. Ciprian Tomuleasa
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  4. Ioana Berindan-Neagoe
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  5. Gabriel Kacso
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  6. Ioan Stefan Florian
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  7. Carmen Crivii
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Corresponding authors

Correspondence to Mihaela Aldea or Lucian Craciun.

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Authors Mihaela Aldea and Lucian Craciun contributed equally to this review.

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Aldea, M., Craciun, L., Tomuleasa, C. et al. Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery. Tumor Biol. 35, 5101–5110 (2014). https://doi.org/10.1007/s13277-014-1676-8

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  • DOI: https://doi.org/10.1007/s13277-014-1676-8

Keywords

  • Cancer
  • Metformin
  • Stem
  • Genetic
  • Nanoparticle
  • Chemoembolization