Phenformin as an Anticancer Agent: Challenges and Prospects

International Journal of Molecular Sciences

Gloria Ruiz Alcalá¹  Esmeralda Carrillo¹  Houria Boulaiz¹  Juan A. Marchal¹  MªEugenia García Rubiño²  Alicia Domínguez-Martín³ 

[1] Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, E-18100 Granada, Spain;Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain;Fundamental Biology Service, Scientific Instrument Center, University of Granada, 18071 Granada, Spain;

关键词: biguanides;    phenformin;    cancer;    diabetes type 2;    cancer stem cells;   

DOI  :  10.3390/ijms20133316

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown