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Phenformin as an Anticancer Agent: Challenges and Prospects

Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, E-18100 Granada, Spain
Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, E-18012 Granada, Spain
Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, 18012 Granada, Spain
Fundamental Biology Service, Scientific Instrument Center, University of Granada, 18071 Granada, Spain
Research Unit “Modeling Nature” (MNat), University of Granada, 18016 Granada, Spain
Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3316;
Received: 11 June 2019 / Revised: 28 June 2019 / Accepted: 3 July 2019 / Published: 5 July 2019
Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop resistance. Phenformin, an oral biguanide drug used to treat type 2 diabetes mellitus, was removed from the market due to a high risk of fatal lactic acidosis. However, it has been shown that phenformin is, with other biguanides, an authentic tumor disruptor, not only by the production of hypoglycemia due to caloric restriction through AMP-activated protein kinase with energy detection (AMPK) but also as a blocker of the mTOR regulatory complex. Moreover, the addition of phenformin eliminates resistance to antiangiogenic tyrosine kinase inhibitors (TKI), which prevent the uncontrolled metabolism of glucose in tumor cells. In this review, we evidence the great potential of phenformin as an anticancer agent. We thoroughly review its mechanism of action and clinical trial assays, specially focusing on current challenges and future perspectives of this promising drug. View Full-Text
Keywords: biguanides; phenformin; cancer; diabetes type 2; cancer stem cells biguanides; phenformin; cancer; diabetes type 2; cancer stem cells
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García Rubiño, M.E.; Carrillo, E.; Ruiz Alcalá, G.; Domínguez-Martín, A.; A. Marchal, J.; Boulaiz, H. Phenformin as an Anticancer Agent: Challenges and Prospects. Int. J. Mol. Sci. 2019, 20, 3316.

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